View source for Piwi

[[Image:1ytu argonaute dsrna.png|thumb|right|The piwi domain of an [[argonaute]] protein with bound [[siRNA]], components of the [[RNA-induced silencing complex]] that mediates [[gene silencing]] by [[RNA interference]].]]

The '''piwi''' (sometimes also '''PIWI'''; originally '''P-element induced wimpy testis''' in ''Drosophila''<ref name="Saito">Saito K, Nishida KM, Mori T, Kawamura Y, Miyoshi K, Nagami T, Siomi H, Siomi MC. (2006). Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. ''Genes Dev'' 20(16):2214-22. PMID 16882972</ref>) class of [[gene]]s was originally identified as encoding [[gene regulation|regulatory]] [[protein]]s responsible for maintaining incomplete [[cell differentiation|differentiation]] in [[stem cell]]s and maintaining the stability of [[cell division]] rates in [[germ line]] cells.<ref name="Cox">Cox DN, Chao A, Lin H. (2000). piwi encodes a nucleoplasmic factor whose activity modulates the number and division rate of germline stem cells. ''Development'' 127(3):503-14. PMID 10631171</ref> Piwi proteins are highly [[conservation (genetics)|conserved]] across [[evolution]]ary lineages and are present in both plants and animals.<ref name="Cox2">Cox DN, Chao A, Baker J, Chang L, Qiao D, Lin H. (1998). A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. ''Genes Dev'' 12(23):3715-27. PMID 9851978</ref> One of the major human [[homology (biology)|homologs]], whose upregulation is implicated in the formation of [[tumor]]s such as [[seminoma]]s, is called ''hiwi'';<ref name="Qiao">Qiao D, Zeeman AM, Deng W, Looijenga LH, Lin H. (2002). Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. ''Oncogene'' 21(25):3988-99. PMID 12037681</ref> other variants on the theme include the ''miwi'' protein in mice.<ref name="Deng">Deng W, Lin H. (2002). miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis. ''Dev Cell'' 2(6):819-30. PMID 12062093 </ref>

==Role in RNA interference==
The ''piwi domain'' is a [[protein domain]] homologous to piwi proteins and present in a large number of [[nucleic acid]]-binding proteins, especially those that bind and cleave [[RNA]]. The best-studied such family of proteins is the [[argonaute]] family; argonautes are [[RNase H]]-like [[enzyme]]s that carry out the [[catalysis|catalytic]] functions of the [[RNA-induced silencing complex]] (RISC). In the well-known cellular process of [[RNA interference]], the argonaute protein in the RISC complex binds [[siRNA|small interfering RNA]] (siRNA) generated from exogenous double-stranded RNA or [[microRNA]] (miRNA) generated from endogenous [[non-coding RNA]], both the [[ribonuclease]] [[dicer]]. The RNA-RISC complex binds and cleaves [[complementarity (molecular biology)|complementary]] [[base pair]]ing [[messenger RNA]], destroying it and preventing its [[translation (genetics)|translation]] into a protein. Crystallized piwi domains have a conserved [[base (chemistry)|basic]] [[binding site]] for the [[5' end]] of bound RNA; in the case of argonaute proteins binding siRNA strands, the last unpaired [[nucleotide]] base of the siRNA is also stabilized by [[base stacking]] interactions between the base and neighboring [[tyrosine]] residues.<ref name="Ma">Ma J, Yuan Y, Meister G, Pei Y, Tuschl T, Patel D (2005). "Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein". ''Nature'' 434 (7033): 666-70. PMID 15800629</ref>

Recent evidence suggests that the germ-line determination function of piwi proteins relies on their interaction with miRNAs, which are known to play a key role in early [[developmental biology|development]] and [[morphogenesis]] of ''[[Drosophila melanogaster]]'' [[embryo]]s, in which germ-line maintenance has been extensively studied.<ref name="Megosh">Megosh HB, Cox DN, Campbell C, Lin H. (2006). The role of PIWI and the miRNA machinery in Drosophila germline determination. ''Curr Biol'' 16(19):1884-94. PMID 16949822 </ref> 

==piRNAs and transposon silencing==
Recently, a novel class of longer-than-average miRNAs known as [[Piwi-interacting RNA]]s (piRNAs) has been defined in [[mammal]]ian cells, about 26-31 [[nucleotide]]s long as compared to the more typical miRNA or siRNA of about 21 nucleotides. These piRNAs are expressed specifically in [[spermatogenesis|spermatogenic]] cells in the [[testes]] of mammals.<ref name="Kim">Kim VN. (2006). Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. ''Genes Dev'' 20(15):1993-7. PMID 16882976 </ref> piRNAs have been identified in the [[genome]]s of [[mouse|mice]], [[rat]]s, and [[human]]s, with an unusual "clustered" genomic organization<ref name="Girard">Girard A, Sachidanandam R, Hannon GJ, Carmell MA. (2006). A germline-specific class of small RNAs binds mammalian Piwi proteins. ''Nature'' 442(7099):199-202. PMID 16751776 </ref> that may originate from repetitive regions of the genome such as [[retrotransposon]]s or regions normally organized into [[heterochromatin]], and which are normally derived exclusively from the [[antisense]] strand of double-stranded RNA.<ref name="Vagin">Vagin VV, Sigova A, Li C, Seitz H, Gvozdev V, Zamore PD. (2006). A distinct small RNA pathway silences selfish genetic elements in the germline. ''Science'' 313(5785):320-4. PMID 16809489 </ref> piRNAs have thus been classified as ''repeat-associated small interfering RNAs'' (rasiRNAs).<ref name="Saito" /> Although their biogenesis is not yet well understood, piRNAs and Piwi proteins are thought to form an endogenous system for silencing the expression of [[selfish gene|selfish genetic elements]] such as retrotransposons and thus preventing the gene products of such sequences from interfering with germ cell formation.<ref name="Vagin" />

==References==
{{reflist|2}}

==External links==
* [http://scop.life.nthu.edu.tw/data/scop.b.d.he.d.ba.A.html SCOP PIWI domain family]

[[Category:Proteins]]
[[Category:Protein domains]]