View source for Nucleohyaloplasm

{{SI}}
'''Editor-In-Chief:''' Henry A. Hoff

==Overview==

A hyaloplasm is the clear, structureless, apparently homogeneous fluid of the cytoplasm. Similar to the hyaloplasm of a cell, the nucleus contains nucleohyaloplasm. It is a highly viscous liquid. This liquid contains [[enzyme]]s (which direct activities that take place in the nucleus), intermediate [[metabolite]]s, and many substances such as [[nucleotide]]s (necessary for purposes as the [[DNA replication|replication of DNA]] and production of [[Messenger RNA|mRNA]]). All are dissolved in the nucleohyaloplasm. It is part of the [[nucleoplasm]] and is partly made up of [[nucleosol]].

==Introduction==

'''Nucleohyaloplasm''' is the [[cytosol]] within the [[nucleus]], without the [[microfilaments]] and the [[microtubules]], also known as [[nucleosol]], vis à vis mitosol and [[cytosol]]<ref name=Solakidi>{{ cite journal |author=Solakidi S, Psarra AM, Sekeris CE |title=Differential distribution of glucocorticoid and estrogen receptor isoforms:localization of GRβ and ERα in nucleoli and GRα and ERβ in the mitochondria of human osteosarcoma SaOS-2 and hepatocarcinoma HepG2 cell lines |journal=J Musculoskelet Neuronal Interact. |volume=7 |issue=3 |pages=240-5 |month=Jul-Sep |year=2007 |url=http://www.ismni.org/jmni/pdf/29/07SOLAKIDI.pdf |pmid=17947807 }}</ref>.

As a cytosol, it consists mostly of [[water]], dissolved ions, small molecules, and large water-soluble molecules (such as [[protein]]). It contains about 20% to 30% protein. It has a high concentration of K⁺ ions and a low concentration of Na⁺ ions. Normal human cytosolic [[pH]] ranges between 7.3 - 7.5, depending on the [[cell type]] involved.<ref name=Roos>{{cite journal |author=Roos A, Boron WF |title=Intracellular pH |journal=Physiol. Rev. |volume=61 |issue=2 |pages=296–434 |year=1981 |month=April |pmid=7012859 |url=http://physrev.physiology.org/cgi/pmidlookup?view=long&pmid=7012859}}</ref>

As a '''plasm''' it contains formative material, portions of the [[nucleoskeleton]] as it is being shaped or reshaped, macromolecules with limited mobility, and portions of the nuclear envelope as it is recycled.

==Small particles==

Small particles (< 40 [[kDa]]<ref name=Naim>{{ cite journal |author=Naim B, Brumfeld V, Kapon R, Kiss V, Nevo R, Reich Z |title=Passive and Facilitated Transport in Nuclear Pore Complexes Is Largely Uncoupled |journal=J Biol Chem. |volume=282 |issue=6 |pages=3881-8 |month=Feb |year=2007 |doi=10.1074/jbc.M608329200 |pmid=17164246 |url=http://www.jbc.org/cgi/content/full/282/6/3881 }}</ref>, <50 kDa<ref name=wiley>{{ cite web |url=http://www3.interscience.wiley.com/journal/114215775/abstract |title=Research highlights |journal=Biopolymers. |volume=86 |issue=2 |year=2007 |month=Apr |page=fmiv |doi=10.1002/bip.20740 }}</ref>, <~70 kDa<ref name=Mahato>{{ cite journal |author=Mahato RI, Rolland A, Tomlinson E |title=Cationic Lipid-Based Gene Delivery Systems: Pharmaceutical Perspectives |journal=Pharm Res. |volume=14 |issue=7 |month=Jul |pages=853-9 |year=1997 |pmid=9244140 }}</ref>, ≤ 70 kDa<ref name=Chesnoy>{{ cite journal |author=Chesnoy S, Huang L |title=STRUCTURE AND FUNCTION OF LIPID-DNA COMPLEXES FOR GENE DELIVERY |journal=Annu Rev Biophys Biomol Struct. |volume=29 |issue= |month=Jun |year=2000 |pages=27-47 |doi=10.1146/annurev.biophys.29.1.27 |pmid=10940242 }}</ref>) are able to pass through the [[nuclear pore]] complex by [[passive transport]]. Larger proteins require a [[nuclear localization signal]] (NLS). The pores are 100 [[nm]] in total diameter, with an opening diameter of about 50 nm; however, the gap through which molecules freely diffuse is only about 9-10 nm wide,<ref name=Kramer>{{ cite journal |author=Kramer A, Ludwig Y, Shahin V, Oberleithner H |title=A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules |journal=J Biol Chem. |volume=282 |issue=43 |pages=31437-43 |month=Oct |year=2007 |doi=10.1074/jbc.M703720200 |pmid=17726020 |url=http://www.jbc.org/cgi/content/full/282/43/31437 }}</ref> due to the presence of regulatory systems within the center of the pore. The 10 nm diameter corresponds to an upper mass limit of 70 kDa.<ref name=Melchior>{{ cite journal |author=Melchior F, Gerace L |title=Mechanisms of nuclear protein import |journal=Curr Opin Cell Biol. |volume=7 |issue=3 |month=Jun |year=1995 |pages=310-8 |pmid=7662359 }}</ref> The majority of the non-protein molecules have a [[molecular mass]] of less than 300&nbsp;[[Atomic mass unit|Da]].<ref name=Goodacre>{{cite journal |author=Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB |title=Metabolomics by numbers: acquiring and understanding global metabolite data |journal=Trends Biotechnol. |volume=22 |issue=5 |pages=245–52 |year=2004 |month=May |pmid=15109811 |doi=10.1016/j.tibtech.2004.03.007 |url=http://personalpages.manchester.ac.uk/staff/roy.goodacre/learning/metabprof/Goodacre-TibTech2004.pdf|format=PDF}}</ref>

This mixture of small molecules is extraordinarily complex, as the variety of molecules that are involved in metabolism (the [[metabolite]]s) is immense. For example up to 200,000 different small molecules might be made in plants, although not all these will be present in the same species, or in a single cell.<ref name=Weckwerth>{{cite journal |author=Weckwerth W |title=Metabolomics in systems biology |journal=Annu Rev Plant Biol |volume=54 |issue= |pages=669–89 |year=2003 |pmid=14503007 |doi=10.1146/annurev.arplant.54.031902.135014}}</ref> Estimates of the number of metabolites in a single cell of ''[[Escherichia coli|E. coli]]'' or [[Saccharomyces cerevisiae|baker's yeast]] predict that under 1,000 are made.<ref name=Reed>{{cite journal |author=Reed JL, Vo TD, Schilling CH, Palsson BO |title=An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR) |journal=Genome Biol. |volume=4 |issue=9 |pages=R54 |year=2003 |pmid=12952533 |pmc=193654 |doi=10.1186/gb-2003-4-9-r54 |url=http://genomebiology.com/1465-6906/4/R54}}</ref><ref name=Förster>{{cite journal |author=Förster J, Famili I, Fu P, Palsson BØ, Nielsen J |title=Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network |journal=Genome Res. |volume=13 |issue=2 |pages=244–53 |year=2003 |month=February |pmid=12566402 |pmc=420374 |doi=10.1101/gr.234503 |url=http://www.genome.org/cgi/pmidlookup?view=long&pmid=12566402}}</ref>

===[[Polymerase]]s===

Many of the subunits of [[RNA polymerase II]] ({{EC number|2.7.7.6}}) are small polymerases. RNA polymerase IIC ([[POLR2C|PolR2C]]) has a mass of 33 kDa, no NLS, is intracellular to the nucleus and is part of the transcription complex. Of the others, PolR2D-L are 19 kDa or less without NLS, except RNA polymerase IIE ([[POLR2E|PolR2E]]) 23 kDa has a NLS and is the only one that localizes to the nucleolus.<ref name=POLR2E>{{ cite web |title=Nuclear Protein Database DNA-directed RNA polymerase II 23 kDa polypeptide |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP01403 }}</ref> Although PolR2K and [[POLR2L|PolR2L]] are small enough in mass to be considered oligopeptides, their numbers of aa are over the usual limit: 58 aa and 67 aa, respectively, in humans.

==Large particles==

Larger particles are also able to pass through the large diameter of a nuclear pore but at almost negligible rates.<ref name=Campbell>{{cite book |last=Campbell |first=Neil A. |title=Biology |year=1987 |isbn=0-8053-1840-2 |pages=795}}</ref> However, the nucleohyaloplasm does contain large amounts of [[macromolecule]]s, which can alter how molecules behave, through [[macromolecular crowding]]. Since some of these macromolecules have less volume to move in, their [[activity (chemistry)|effective concentration]] is increased. This crowding effect can produce large changes in both the [[reaction rate|rates]] and [[chemical equilibrium]] for reactions in the nucleohyaloplasm.<ref name=Ellis>{{cite journal |author=Ellis RJ |title=Macromolecular crowding: obvious but underappreciated |journal=Trends Biochem. Sci. |volume=26 |issue=10 |pages=597–604 |year=2001 |month=October |pmid=11590012 |doi=10.1016/S0968-0004(01)01938-7}}</ref> It is particularly important in its ability to alter [[dissociation constant]]s by favoring the association of macromolecules, such as when multiple proteins come together to form [[protein complex]]es, or when [[DNA-binding protein]]s bind to their targets in the [[genome]].<ref name=Zhou>{{cite journal |author=Zhou HX, Rivas G, Minton AP |title=Macromolecular crowding and confinement: biochemical, biophysical, and potential physiological consequences |journal=Annu Rev Biophys |volume=37 |issue= |pages=375–97 |year=2008 |pmid=18573087 |doi=10.1146/annurev.biophys.37.032807.125817}}</ref>

===Proteins===

Proteins larger than those allowed through a nuclear pore by passive transport require a [[nuclear localization signal]] (NLS). This is an amino acid sequence that targets the cytosolic nuclear transport receptors of the [[Nuclear pore|nuclear pore complex]]. A nuclear import NLS will bind strongly to [[importin]], while an export NLS ([[nuclear export signal]], NES) binds to an [[exportin]]. For example, [[RNA polymerase II]]A (Rbp1) 220kDa has a NLS.<ref name=POLR2A>{{ cite web |title=Nuclear Protein Database: DNA-directed RNA polymerase II largest subunit |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP01404 | accessdate = }}</ref>

===Nuclear localization===

The subcellular distribution of a substance to or within the nucleus is often referred to as '''nuclear localization'''.<ref name=Nieva>{{ cite journal |author=Nieva C, Gwoźdź T, Dutko-Gwoźdź J, Wiedenmann J, Spindler-Barth M, Wieczorek E, Dobrucki J, Duś D, Henrich V, Ożyhar A, Spindler KD |title=Ultraspiracle promotes the nuclear localization of ecdysteroid receptor in mammalian cells |year=2005 |journal=Biol Chem. |volume=386 |issue=5 |pages=463-70 |doi=10.1515/BC.2005.055 }}</ref> Many mechanisms have been found that produce nuclear localization in addition to a NLS.

[[PLAGL1|Zac1]] is a seven-zinc-finger transcription factor that preferentially binds GC-rich DNA elements and has intrinsic transactivation activity.<ref name=Huang>{{ cite journal |author=Huang SM, Huang SP, Wang SL, Liu PY |title=Importin α1 is involved in the nuclear localization of Zac1 and the induction of p21WAF1/CIP1 by Zac1 |journal=Biochem J. |volume=402 |issue=Pt 2 |month=Mar |year=2007 |pages=359-66 |doi=10.1042/BJ20061295 |pmid=17109628 }}</ref> The zinc-finger motif is of a Cys<sub>2</sub>His<sub>2</sub>-type.<ref name=Huang/> This motif is involved in [[DNA-binding domain|DNA binding]], [[Dimer|dimerization]], [[transactivation]] activity, and nuclear localization of Zac1 through interacting with [[importin]] α<sub>1</sub>.<ref name=Huang/> Zac1 has no typical NLS.<ref name=Huang/> Any two or more zinc-finger motifs act in concert to facilitate nuclear localization.<ref name=Huang/> Apparently, as with importin α transport of [[Ca2+/calmodulin-dependent protein kinase|CaMKIV]] to the nucleus, importin α<sub>1</sub> may mediate transport of Zac1 to the nucleus without the involvement of [[Nuclear pore|importin β]].<ref name=Huang/> But, some other factors are involved, perhaps Ran-binding proteins such as [[RANBP9|RanBPM]] and Mog1<ref name=RANGRF>{{ cite web |title=Entrez Gene: RANGRF RAN guanine nucleotide release factor |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=29098&ordinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref>, which play roles in nucleocytoplasmic transport and [[transcription factor]] recruitment.<ref name=Huang/>

===[[Transcription (genetics)#Transcription factories|Transcription factories]]===

Active transcription units are clustered in the nucleus, in discrete sites called ‘transcription factories’. Such sites can be visualized after allowing engaged polymerases to extend their transcripts in tagged precursors (Br-UTP or Br-U), and immuno-labeling the tagged nascent RNA. Transcription factories can also be localized using fluorescence in situ hybridization, or marked by antibodies directed against polymerases. There are ~8,000 [[RNA polymerase II|polymerase II]] factories in the nucleoplasm of a [[HeLa cell]]. Each polymerase II factory contains ~8 polymerases. As most active transcription units are associated with only one polymerase, each factory can be associated with ~8 different transcription units. That's ~64,000 polymerase II active transcription units. These units might be associated through promoters and/or enhancers, with loops forming a ‘cloud’ around the factory.

===[[RNA]]===

Of the many different types of RNA that can occur within a cell, most also can occur dissolved in the nucleohyaloplasm. In addition to [[Messenger RNA|mRNA]], which is constructed during gene transcription to produce protein, there are a variety of RNAs that are transcripted from genes for their own sake into the nucleohyaloplasm: [[ribosomal RNA]] (rRNA), [[transfer RNA]] (tRNA), [[small nuclear RNA]] (snRNA), [[small nucleolar RNA]] (snRNA), [[non-coding RNA]] (ncRNA), miscRNA<ref name= DISC2 >{{cite web | title = Entrez Gene: DISC2 disrupted in schizophrenia 2 (non-protein coding)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27184| accessdate = }}</ref>, [[microRNA]], [[piwi-interacting RNA]] (piRNA), [[small interfering RNA]] (siRNA), [[7SL RNA|signal recognition particle RNA]] (SRP RNA), and [[guide RNA]] (gRNA).

Each has to be [[Transcription (genetics)|transcribed]] from the applicable portion of [[DNA]] in the [[euchromatin]]. The unfolded structure of euchromatin allows gene regulatory proteins and [[RNA polymerase]] (RNAP) complexes to bind to the DNA sequence, which can then initiate the transcription process. Control of the process of gene transcription affects patterns of gene expression and thereby allows a cell to adapt to a changing environment, perform specialized roles within an organism, and maintain basic metabolic processes necessary for survival. RNAP can initiate [[transcription]] at specific DNA sequences known as [[promoter]]s. It then produces an RNA chain which is [[Complementarity (molecular biology)|complementary]] to the template DNA strand.

{| class="wikitable sortable"
|+ RNAs involved in protein synthesis
|-
! Type !! Abbr. !! Function !! Distribution !! Ref.
|-
| [[Messenger RNA]] || mRNA || [[Genetic code|Codes]] for protein  || All cells
|-
| [[Ribosomal RNA]] || rRNA || [[Translation (genetics)|Translation]] || All cells
|-
| [[7SL RNA|Signal recognition particle RNA]] || 7SL RNA or SRP RNA|| Membrane integration / mRNA tagging for export|| All organisms ||<ref name= Gribaldo >{{cite journal | author=Gribaldo S, Brochier-Armanet C| title=The origin and evolution of Archaea: a state of the art| journal=Philos Trans R Soc Lond B Biol Sci.| year=2006| volume=361 | issue=1470| pages=1007–22| pmid=16754611| doi=10.1098/rstb.2006.1841}}</ref>
|-
| [[Transfer RNA]] || tRNA || Translation || All cells
|-
| [[tmRNA|Transfer-messenger RNA]] || tmRNA || Rescuing stalled ribosomes Terminating translation || Bacteria ||<ref name=Gillet>{{cite journal | author=Gillet R, Felden B| title=Emerging views on tmRNA-mediated protein tagging and ribosome rescue | journal = Molecular Microbiology| volume=42| issue=4 | pages=879–85| year=2001| doi=10.1046/j.1365-2958.2001.02701.x }}</ref>
|-
|}

{| class="wikitable sortable"
|+ RNAs involved in post-transcriptional modification or DNA replication
|-
! Type !! Abbr. !! Function !! Distribution !! Ref.
|-
| [[Small nuclear RNA]] || snRNA || Splicing and other functions || [[Eukaryote]]s and [[archaea]] ||<ref name= Thore >{{cite journal | author=Thore S, Mayer C, Sauter C, Weeks S, Suck D| title=Crystal Structures of the ''Pyrococcus abyssi'' Sm Core and Its Complex with RNA | journal=J. Biol. Chem.| year=2003| volume=278| issue=2| pages=1239–47| doi=10.1074/jbc.M207685200 |url=http://www.jbc.org/cgi/content/full/278/2/1239 }}</ref>
|-
| [[Small nucleolar RNA]] || snoRNA || Nucleotide modification of RNAs [[RNA editing]] || Eukaryotes and archaea ||<ref name=Kiss>{{cite journal | author=Kiss T| title=Small nucleolar RNA-guided post-transcriptional modification of cellular RNAs| journal=The EMBO Journal| year=2001| volume=20| pages=3617–22| doi=10.1093/emboj/20.14.3617 |url=http://www.nature.com/emboj/journal/v20/n14/full/7593858a.html}}</ref>
|-
| [[SmY RNA]] || SmY || mRNA trans-splicing || Nematodes || <ref name=Jones>{{cite journal |author=Jones TA, Otto W, Marz M, Eddy SR, Stadler PF |title=A survey of nematode SmY RNAs |journal=RNA Biol |volume=6 |issue=1 |pages=5–8 |year=2009 |pmid=19106623 |doi= |url=http://www.landesbioscience.com/journals/rna/abstract.php?id=7634}}</ref>
|-
| [[Small Cajal body-specific RNA]] || scaRNA || Type of snoRNA; Nucleotide modification of RNAs || ||
|-
| [[Guide RNA]] || gRNA || mRNA nucleotide modification / [[RNA editing]] || [[Kinetoplastid]] [[mitochondria]] ||<ref name=Alfonzo>{{cite journal | author=Alfonzo JD, Thiemann O, Simpson L | title=The mechanism of U insertion/deletion RNA editing in kinetoplastid mitochondria| journal=Nucleic Acids Research| year=1997| volume=25| issue=19| pages=3751–59| pmid=9380494 | doi=10.1093/nar/25.19.3751 |url=http://nar.oxfordjournals.org/cgi/content/abstract/25/19/3751}}</ref>
|-
| [[RNase P|Ribonuclease P]] || RNase P || tRNA maturation || All organisms ||<ref>{{cite journal | author=Pannucci JA, Haas ES, Hall TA, Harris JK, Brown JW| title=RNase P RNAs from some Archaea are catalytically active | journal=Proc Natl Acad Sci USA| year=1999| volume=96 | issue=14| pages=7803–08| pmid=10393902| doi=10.1073/pnas.96.14.7803}}</ref>
|-
| [[RNase MRP|Ribonuclease MRP]] || RNase MRP || rRNA maturation, [[DNA replication]] || Eukaryotes ||<ref>{{cite journal | author=Woodhams MD, Stadler PF, Penny D, Collins LJ| title=RNase MRP and the RNA processing cascade in the eukaryotic ancestor| journal=BMC Evolutionary Biology| year=2007| volume=7| pages=S13| doi=10.1186/1471-2148-7-S1-S13}}</ref>
|-
| [[Y RNA]] || || RNA processing, DNA replication || Animals ||<ref>{{cite journal | author=Perreault J, Perreault J-P, Boire G| title=Ro-associated Y RNAs in metazoans: evolution and diversification| journal=Molecular Biology and Evolution | year=2007 | volume=24| issue=8| pages=1678–89 | doi=10.1093/molbev/msm084}}</ref>
|-
| [[Telomerase RNA]] || || [[Telomere]] synthesis || Most eukaryotes ||<ref>{{cite journal | author=Lustig AJ| title=Crisis intervention: The role of telomerase| journal=Proc Natl Acad Sci USA | year=1999| volume=96| issue=7| pages=3339–41| pmid=10097039| doi=10.1073/pnas.96.7.3339}}</ref>
|-
| [[Ribozyme]] || || [[Catalysis]] || All cells
|-
| [[Transposon]] || || Self-propagating || All cells
|-
|}

{| class="wikitable sortable"
|+ Regulatory RNAs
|-
! Type !! Abbr. !! Function !! Distribution !! Ref.
|-
| [[Antisense RNA]] || aRNA || Transcriptional attenuation / mRNA degradation / mRNA stabilisation / Translation block Gene regulation || All organisms ||<ref name=Brantl1>{{cite journal | author=Brantl S| title=Antisense-RNA regulation and RNA interference| journal=Biochimica et Biophysica Acta| year=2002| volume=1575| issue=1–3| pages=15–25| pmid=12020814}}</ref><ref name=Brantl2>{{cite journal |author=Brantl S |title=Regulatory mechanisms employed by cis-encoded antisense RNAs |journal=Curr Opin Microbiol. |volume=10 |issue=2 |pages=102–9 |year=2007 |pmid=17387036 |doi=10.1016/j.mib.2007.03.012}}</ref>
|-
| [[Cis-natural antisense transcript]] || || Gene regulation || ||
|-
| [[CRISPR]] RNA || crRNA || Resistance to parasites, probably by targeting their DNA || Bacteria and archaea ||<ref>{{cite journal |author=Brouns SJ, Jore MM, Lundgren M, ''et al'' |title=Small CRISPR RNAs guide antiviral defense in prokaryotes |journal=Science (New York, N.Y.) |volume=321 |issue=5891 |pages=960–4 |year=2008 |month=August |pmid=18703739 |doi=10.1126/science.1159689}}</ref>
|-
| [[Long noncoding RNA]] || Long&nbsp;ncRNA || Various || Eukaryotes ||
|-
| [[MicroRNA]] || miRNA || Gene regulation || Most eukaryotes ||<ref name=Lin>{{cite journal | author=Lin S-L, Miller JD, Ying S-Y| title=Intronic microRNA (miRNA)| journal=Journal of Biomedicine and Biotechnology| year=2006 |pages=1–13| pmid=17057362| doi=10.1155/JBB/2006/26818| volume=2006}}</ref>
|-
| [[Piwi-interacting RNA]] || piRNA || Transposon defense Gene regulation|| Animal [[germline]] cells ||<ref name=Horwich>{{cite journal | author=Horwich MD, Li C Matranga C, Vagin V, Farley G, Wang P, Zamore PD| title=The ''Drosophila'' RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC| journal=Current Biology| year=2007| volume=17| pages=1265–72| doi=10.1016/j.cub.2007.06.030}}</ref><ref name=Ghildiyal>{{cite journal |author=Ghildiyal M, Zamore PD |title=Small silencing RNAs: an expanding universe |journal=Nat. Rev. Genet. |volume=10 |issue=2 |pages=94–108 |year=2009 |month=February |pmid=19148191 |doi=10.1038/nrg2504}}</ref>
|-
| [[Small interfering RNA]] || siRNA || Gene regulation || Most [[eukaryote]]s ||<ref name=Ahmad>{{cite journal | author=Ahmad K, Henikoff S | title=Epigenetic consequences of nucleosome dynamics | journal=Cell| year=2002| volume=111 | issue=3| pages=281–84| doi=10.1016/S0092-8674(02)01081-4}}</ref>
|-
| [[Trans-acting siRNA]] || tasiRNA || Gene regulation || Land plants||<ref>{{cite journal | author=Vazquez F, Vaucheret H| title=Endogenous trans-acting siRNAs regulate the accumulation of Arabidopsis mRNAs| journal=Mol. Cell| issue=16 | year=2004 |pages=1–13| pmid=17057362}}</ref>
|-
| [[rasiRNA|Repeat associated siRNA]] || rasiRNA || Type of piRNA; transposon defense|| Drosophila || <ref>{{cite journal |author=Desset S, Buchon N, Meignin C, Coiffet M, Vaury C |title=In Drosophila melanogaster the COM locus directs the somatic silencing of two retrotransposons through both Piwi-dependent and -independent pathways |journal=PLoS ONE |volume=3 |issue=2 |pages=e1526 |year=2008 |pmid=18253480 |pmc=2211404 |doi=10.1371/journal.pone.0001526}}</ref>
|-
|}

[[Ribozyme]]s are transcripted into the nucleohyaloplasm. The functional part of the ribosome, the molecular machine that translates RNA into proteins, is fundamentally a ribozyme. Ribozymes often have divalent metal ions such as Mg<sup>2+</sup> as cofactors. Ribozyme RNase P 30kDa has a NLS.<ref name=RNaseP>{{ cite web |title=Nuclear Protein Database: Rnase P 30kD |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP00372 |accessdate= }}</ref> But, RNase P subunit p25 (25 kDa), which is also localized to the nucleolus does not.<ref name=RPP25>{{ cite web |title=Nuclear Protein Database: RPP25 |url=https://npd.hgu.mrc.ac.uk/search.php?action=builddetails&geneid=1NP02179 |accessdate= }}</ref>

Probably the largest mRNA transcripted into the nucleohyaloplasm is from the gene for [[dystrophin]] (427 kDA protein). The primary transcript measures 2.4 megabases (thus the gene comprises 0.008% of the human genome), and takes 16 hours to transcribe. The 79 exons code for a protein of 3685 amino acid residues. Its mRNA is 14 kb or ~550 kDa.

===[[Chromatin]]===

[[Euchromatin]] is the less compact DNA form, and contains genes that are frequently [[gene expression|expressed]] by the cell.<ref name=Ehrenhofer-Murray>{{cite  journal  | author = Ehrenhofer-Murray A | title = Chromatin dynamics at DNA replication, transcription and repair | journal = Eur J Biochem | volume = 271 | issue = 12 | pages = 2335–2349 | year = 2004 | pmid = 15182349 | doi = 10.1111/j.1432-1033.2004.04162.x  }}</ref> Active genes, which are generally found in the euchromatic region of the chromosome, tend to be located towards the chromosome's territory boundary.<ref name=Kurz>{{cite journal  |author= Kurz A , Lampel S,  Nickolenko JE, Bradl J, Benner A, Zirbel RM, Cremer T, Lichter P |title = Active and inactive genes localize preferentially in the periphery of chromosome territories  |doi = 10.1083/jcb.135.5.1195 | journal = J of Cell Biol.  |volume=135  |issue =   | pages =1195–1205  | publisher = The Rockefeller University Press | year = 1996 | url = http://intl.jcb.org/cgi/content/abstract/135/5/1195 | pmid =8947544 }}</ref>

[[Heterochromatin]] is usually localized to the periphery of the nucleus along the nuclear envelope. It mainly consists of genetically inactive [[satellite DNA|satellite sequences]],<ref name=Lohe>{{cite journal| author = Lohe, A.R., ''et al.''| title = Mapping simple repeated DNA sequences in heterochromatin of ''Drosophila melanogaster''| year = 1993| journal = [[Genetics (journal)|Genetics]]| volume = 134| issue = 4| pages = 1149–1174| issn = 0016-6731| url = http://www.genetics.org/cgi/content/full/134/4/1149| pmid = 8375654}}</ref> and many genes are repressed to various extents, although some cannot be expressed in euchromatin at all.<ref name=Lu>{{cite journal| author = Lu, B.Y., ''et al.''| year = 2000| title = Heterochromatin protein 1 is required for the normal expression of two heterochromatin genes in Drosophila| journal = [[Genetics (journal)|Genetics]]| volume = 155| issue = 2| pages = 699–708| url = http://www.genetics.org/cgi/content/full/155/2/699| issn = 0016-6731| pmid = 10835392}}</ref>

====Mobile chromatin====

During [[interphase]] euchromatin is known to be attached to the nucleolus or nucleoli and heterochromatin is attached to the nuclear envelope.<ref name=Abney>{{ cite journal |author=Abney JR, Cutler B, Fillbach ML, Axelrod D, Scalettar BA |title=Chromatin Dynamics in Interphase Nuclei and Its Implications for Nuclear Structure |journal=J Cell Biol. |volume=137 |issue=7 |pages=1459-68 |month=Jun |year=1997 |pmid=2137814 }}</ref> Further, in some cell types interphase euchromatin and heterochromatin are translationally immobile over distances ≥400 nm.<ref name=Abney/> Mobile chromatin can move with velocities averaging 50-70 nm/sec.<ref name=Eskiw>{{ cite journal |author=Eskiw CH, Dellaire G, Mymryk JS, Bazett-Jones DP |title=Size, position and dynamic behavior of PML nuclear bodies following cell stress as a paradigm for supramolecular trafficking and assembly |journal=J Cell Sci. |volume=116 |issue=Pt 21 |month=Nov |pages=4455-66 |year=2003 |doi=10.1242/jcs.00758 |pmid= 13130097 }}</ref>

===[[Nucleolus]]===

The nucleolus is roughly spherical, and is surrounded by the euchromatin. No membrane separates the nucleolus from the nucleohyaloplasm. Nucleoli carry out the production and maturation of [[ribosome]]s. Large numbers of ribosomes are found inside.

Direct contact between the nucleolus and the [[nuclear envelope]] is frequently observed but is not dependent on nucleolar activity.<ref name=Schwarzacher>{{ cite journal |author=Schwarzacher HG, Wachtler F |title=The nucleolus |journal=Anat Embryol (Berl). |volume=188 |issue=6 |year=1993 |month=Dec |pages=515-36 |pmid=8129175 }}</ref>

Although the size of the nucleolus is highly variable in any particular cell nucleus, there is in some cells a correlation with cell diameter: increasing cell size to increasing rounded diameter of the nucleolus.<ref name=Coggeshall>{{ cite journal |author=Coggeshall RE, Chung K, Bee DE |title=The relation of nucleolus diameter to cell body diameter in mammalian dorsal root ganglion cells |journal=Anat Rec. |volume=211 |issue=2 |year=1985 |pages=213-7 |month=Feb |pmid= 3977089 }}</ref> Based on this correlation, for an average mammalian cell of 6000 nm, the nucleolus would be ~300 nm in diameter. Interferometric analysis of nucleolus mass for mesothelial cells in culture places its mass average at 40 x 10<sup>-12</sup> gm (40 pgm)<ref name=Blumenstein>{{ cite journal |author=Blumenstein R, Amenta PS |title=An interferometric analysis of nucleoli in cultured mesothelial cells
|journal=Anat Rec. |volume=201 |issue=1 |pages=13-21 |year=1981 |month=Sep |pmid=7030143 |doi=10.1002/ar.1092010103 }}</ref> or approximately 24 TDa (teradaltons).  In addition, each cell may have approximately the same total nucleolar mass regardless of the number of nucleoli.<ref name=Blumenstein/>

==Structures==

Of the structures local to the nucleohyaloplasm, some serve to confine it such as the inner membrane of the [[nuclear envelope]]. While others are completely suspended within it, for example, the [[nucleolus]]. Still others such as the [[nuclear matrix]]<ref name=Nickerson>{{cite journal |author=Nickerson J |title=Experimental observations of a nuclear matrix |journal=J. Cell. Sci. |volume=114 |issue=Pt 3 |pages=463–74 |year=2001 |month=February |pmid=11171316 |url=http://jcs.biologists.org/cgi/content/abstract/114/3/463}}</ref><ref name=Tetko>{{cite journal |author=Tetko IV, Haberer G, Rudd S, Meyers B, Mewes HW, Mayer KF |title=Spatiotemporal expression control correlates with intragenic scaffold matrix attachment regions (S/MARs) in Arabidopsis thaliana |journal=PLoS Comput. Biol. |volume=2 |issue=3 |pages=e21 |year=2006 |month=March |pmid=16604187 |pmc=1420657 |doi=10.1371/journal.pcbi.0020021 }}</ref> and [[nuclear lamina]] are found throughout the inside of the nucleus, some as part of the [[nucleoskeleton]].

Besides the nucleolus, the [[Cell nucleus|nucleus]] contains a number of other non-membrane delineated bodies. These include [[Cajal body|Cajal bodies]], Gemini of coiled bodies, polymorphic interphase karyosomal association (PIKA), promyelocytic leukaemia (PML) bodies, [[paraspeckle]]s and splicing speckles. Although little is known about a number of these domains, they are significant in that they show that the nucleohyaloplasm is not a uniform mixture, but rather contains organized functional subdomains.<ref name=Dundr>{{cite  journal |author= Dundr M, Misteli T |title = Functional architecture in the cell nucleus | journal = Biochem J. | issue = 356 | pages = 297–310 | year = 2001 | pmid = 11368755 | doi = 10.1146/annurev.cellbio.20.010403.103738}}</ref>

==Intra-nuclear transport==

The [[Nucleosol#Average speed for water molecules|lateral speed of a water molecule]] is ~35 µm/sec. The lateral speed of larger biological molecules in [[Passive transport|passive diffusion]] in water is on the order of 500 - 50 nm/sec. But in cytosol such as the nucleohyaloplasm: ~120 - 10 nm/sec due to crowding and collisions with large molecules. In [[mammal]]ian cells, the average diameter of the nucleus is approximately 6 μm.<ref name=Alberts>{{cite book | year = 2002 | title = Molecular Biology of the Cell, Chapter 4, pages 191-234 | editor = Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter | publisher = Garland Science | edition = 4th}}</ref> The large amount of DNA and RNA should hinder the migration of nuclear proteins, but a protein could traverse the entire diameter of a nucleus in a matter of minutes.<ref name=Misteli>{{ cite journal |author=Misteli T |title=Protein dynamics: implications for nuclear architecture and gene expression |journal=Science. |volume=291 |issue=5505 |month=Feb |pages=843-7 |year=2001 |pmid=11225636 }}</ref>

Proteins are frequently transported across the cytosol, along well-defined routes, and delivered to particular addresses. Passive diffusion cannot account for the rate, directionality, or destination of such transport. [[Microtubule]]s function as tracks and the movement is propelled by [[motor protein]]s. Movement can occur in both directions and at velocities between ~5 and 3000 nm/sec.<ref name=Lodish>{{ cite book | author=Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell JE |title=Molecular Cell Biology |publisher=WH Freeman and Company |location=New York | isbn=0-7167-3136-3 |year 2000 |edition=4th |url=http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=transport,Intracellular&rid=mcb.section.5452 }}</ref> One motor protein that localizes intracellularly to the nucleus is myosin 1F ({{Gene|MYO1F}}) 125 kDa.<ref name=MYO1F>{{ cite web |title=GENATLAS : GENE Database MYO1F |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> It does not have a NLS. Its N terminal motor domain uses ATP and has actin binding sites.<ref name=MYO1F/>

All Cajal bodies move through the nucleohyaloplasm.<ref name=Platani>{{ cite journal |author=Platani M, Goldberg I, Swedlow JR, Lamond AI |title=In Vivo Analysis of Cajal Body Movement, Separation, and Joining in Live Human Cells |journal=J Cell Biol. |volume=151 |issue=7 |pages=1561-74 |year=2000 |month=Dec |doi=10.1083/jcb.151.7.1561 |pmid= 11134083 }}</ref> These movements include translocations and moving to or from the nucleolus at velocities of ~10-15 nm/sec.<ref name=Platani/>

Constrained microstructures (~40-100 nm in size, on the order of 0.5-5 [[Atomic mass unit|MDa]]) move with velocities averaging 50-70 nm/sec (comparable to that of mobile chromatin), but free-moving microstructures (in chromatin-free channels) can move at speeds of up to 500 nm/sec.<ref name=Eskiw/> The movement of PML-containing microstructures is energy-independent.<ref name=Eskiw/> Such mobility is characteristic of constrained diffusion.<ref name=Eskiw/>

The movement of elongated chromosomes throughout the chromatin filled nucleus may be associated with intranuclear motor protein action.<ref name=Scherthan>{{ cite book |author=Scherthan H, Orr-Weaver T, Arana P, Gill B |page=225 |title=Meiotic mobility and recombination |pages=215-248 |editor=Henriques-Gil N, Parker JS, Puertas MJ |proceedings title=Chromosomes Today |volume=12 |year=1997 |publisher=Springer |isbn=0412752409, 9780412752407 }}</ref>

==[[Human]] nucleohyaloplasm==

The [[human genome]] contains many of the genes discussed in the sections above regarding the structure, composition, and physiology of the nucleohyaloplasm. These genes and comparable ones in similar species help to understand [[human evolutionary genetics]].

Mature [[monocyte]]s circulating in human [[Venous blood|peripheral blood]] contain multiple nucleoli of various sizes in one and the same nucleus.<ref name=Smetana>{{ cite journal |author=Smetana K, Jirásková I, Otevrelová P, Kalousek I |title=The RNA content of nucleolar bodies is related to their size - a cytochemical study on human monocytes and lymphocytes in blood smears and blood cytospins |journal=Folia Biol (Praha). |volume=54 |issue=4 |pages=130-3 |year=2008 |pmid=18808739 }}</ref> The nucleolar RNA content is apparently related to the nucleolar size.<ref name=Smetana/>

Increases in the number of nucleoli, their size, and their activity reflect the proliferating activity of exponentially growing cells.<ref name=Horky>{{ cite journal |author=Horký M, Kotala V, Anton M, Wesierska-Gadek J |title=Nucleolus and apoptosis |journal=Ann N Y Acad Sci. |volume=973 |month=Nov |pages=258-64 |year=2002 |pmid=12485873 }}</ref>

==Acknowledgements==

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from [http://www.wikipedia.org Wikipedia].

==References==

{{reflist|2}}

==See also==

{{AminoAcids}}
{{Amino acid metabolism enzymes}}
{{MetabolismMap}}
{{Nucleotide metabolism}}
{{Protein biosynthesis}}
{{Protein metabolism}}
{{Protein primary structure}}
{{Protein topics}}


[[Category:Cell anatomy]]


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