- Piwi
The piwi (sometimes also PIWI; originally P-element induced wimpy testis in "Drosophila"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] ) class of
gene s was originally identified as encoding regulatoryprotein s responsible for maintaining incomplete differentiation instem cell s and maintaining the stability ofcell division rates ingerm line cells.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] Piwi proteins are highly conserved acrossevolution ary lineages and are present in both plants and animals.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] One of the major human homologs, whose upregulation is implicated in the formation oftumor s such asseminoma s, is called "hiwi";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] other variants on the theme include the "miwi" protein in mice.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 ]Role in RNA interference
The "piwi domain" is a
protein domain homologous to piwi proteins and present in a large number ofnucleic acid -binding proteins, especially those that bind and cleaveRNA . The best-studied such family of proteins is theargonaute family; argonautes areRNase H -likeenzyme s that carry out the catalytic functions of theRNA-induced silencing complex (RISC). In the well-known cellular process ofRNA interference , the argonaute protein in the RISC complex binds small interfering RNA (siRNA) generated from exogenous double-stranded RNA ormicroRNA (miRNA) generated from endogenousnon-coding RNA , both theribonuclease dicer . The RNA-RISC complex binds and cleaves complementarybase pair ingmessenger RNA , destroying it and preventing its translation into a protein. Crystallized piwi domains have a conserved basicbinding site for the5' end of bound RNA; in the case of argonaute proteins binding siRNA strands, the last unpairednucleotide base of the siRNA is also stabilized bybase stacking interactions between the base and neighboringtyrosine residues.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]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 development and
morphogenesis of "Drosophila melanogaster "embryo s, in which germ-line maintenance has been extensively studied.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 ]piRNAs and transposon silencing
Recently, a novel class of longer-than-average miRNAs known as
Piwi-interacting RNA s (piRNAs) has been defined inmammal ian cells, about 26-31nucleotide s long as compared to the more typical miRNA or siRNA of about 21 nucleotides. These piRNAs are expressed specifically in spermatogenic cells in thetestes of mammals.Kim VN. (2006). Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes. "Genes Dev" 20(15):1993-7. PMID 16882976 ] piRNAs have been identified in thegenome s of mice,rat s, andhuman s, with an unusual "clustered" genomic organizationGirard 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 ] that may originate from repetitive regions of the genome such asretrotransposon s or regions normally organized intoheterochromatin , and which are normally derived exclusively from theantisense strand of double-stranded RNA.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 ] piRNAs have thus been classified as "repeat-associated small interfering RNAs" (rasiRNAs). 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 genetic elements such as retrotransposons and thus preventing the gene products of such sequences from interfering with germ cell formation.References
External links
* [http://scop.life.nthu.edu.tw/data/scop.b.d.he.d.ba.A.html SCOP PIWI domain family]
* - Piwi domain inPROSITE
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