piRNA的发生和相关蛋白的研究进展

摘要/Abstract

摘要：

小RNA能在多水平（染色体构建、转录、翻译、RNA修饰和稳定等）对基因的表达进行调控。piRNA（Piwi－interacting RNA）主要参与生殖细胞的发育、转座子的沉默、异染色质的形成和生殖细胞DNA完整性的维持等过程，对遗传物质的稳定遗传具有重要意义。作为一类新型的小RNA，piRNA受到了广泛关注。从2006年发现至今，科研工作者对piRNA的发生和功能做了大量的推测、探索和验证。研究发现，piRNA主要分布在动物体睾丸的精原细胞和卵巢的卵母细胞内，果蝇卵巢体细胞（卵泡细胞）也存在少量的piRNA。piRNA在生殖细胞和体细胞内通过不同的途径产生，体细胞途径相对简单，生殖细胞途径主要通过“乒乓循环”实现。参与“乒乓循环”的3种Argonaute蛋白中，Piwi位于细胞核中，Ago3和Aub位于细胞质中，这一现象暗示piRNA可能在不同的区室内产生并发挥功能。piRNA 3′端的甲基化现象普遍存在，这对piRNA的稳定性具有重要意义，但并不是决定成熟piRNA长度的必需条件。piRNA相关蛋白质的已知功能是预测其产生过程和功能的重要线索，目前已有部分与piRNA产生和功能相关的蛋白质被发掘。另外，piRNA的调控网络比siRNA（Small interference RNA）和miRNA（microRNA）更加复杂，因此新的研究方法体系的出现加快了科研工作者对piRNA发生和功能的研究进程。本文主要就piRNA的生物发生、产生和功能相关蛋白及研究方法的研究进展做一简要论述。

Abstract:

Small RNAs regulate gene expression at multi-level, such as chromosome construction, transcription, translation, RNA modification and stability. piRNA (Piwi-interacting RNA) mainly participates in the process of development of germ cells, scilence of transposon, formation of heterochromatin, DNA integrity of germ cells, and so on. It is significant to steady heredity of hereditary substance. As a novel small RNA, piRNA has received wide attention. Since piRNA was found in 2006, considerable inference, quest and verification about the biogenesis and function of piRNA have been carried out by researchers. Studies found that piRNA mainly distributed in the animal testes spermatogonial cells and ovarian oocytes, and there are also a small number of piRNAs in Drosophila ovarian somatic cells (follicle cells). piRNA is generated by different ways in germ cells and somatic cells. The way in somatic cells is relatively simpler than that in germ cells, the way in germ cells is mainly through the “ping-pong cycle”. In the “ping-pong cycle”, Piwi locate in the nucleus, Ago3 and Aub locate in the cytoplasm. This phenomenon imply the piRNA may generate and play function in different compartments. The 3′ end hypermethylation of piRNA is widespread, which is significant to the stability of piRNA, but not the necessary conditions to determine the length of of mature piRNAs. Known fuctions of piRNA-related proteins are important clues to predict the biogenesis and fuctions of piRNA. At present, some proteins related to piRNA biogenesis and function have been discovered. piRNA expression is limited to germline cells and its regulatory network is more complex than that of siRNA (small interference RNA) and miRNA (microRNA). The emergence of novel methodology and system speed up the research process of piRNA biogenesis and function. This article is a brief overview focusing on piRNA biogenesis, produce and function related proteins and research methods.

中图分类号:

S813.3
Q752

刘雪青，杨浩，王建刚，曹斌云. piRNA的发生和相关蛋白的研究进展[J]. 畜牧兽医学报, doi: .

LIU Xue-qing, YANG Hao, WANG Jian-gang, CAO Bin-yun. Research Progress on the Biogenesis and Related Proteins of piRNA[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, doi: .

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https://www.xmsyxb.com/CN/Y2012/V43/I12/1855

参考文献

［1］LEE R C, FEINBAUM R L, AMBROS V. The C. elegans heterochronic gene lin-4 encondes small RNAs with antisense complementarity to lin-14 ［J］. Cell, 1993, 75(5): 843-854. ［2］SIOMI H, SIOMI M C. On the road to reading the RNA-interference code ［J］. Nature, 2009, 457(7228): 396-404.

［3］GIRARD A, SACHIDANANDAM R, HANNON G J, et al. A germline-specific class of small RNAs binds mammalian Piwi proteins ［J］. Nature, 2006, 442(7099): 199-202.

［4］ARAVIN A, GAIDATZIS D, PFEFFER S, et al. A novel class of small RNAs bind to MILI protein in mouse testes ［J］. Nature, 2006, 442(7099): 203-207.

［5］LAU N C, SETO A G, KIM J, et al. Characterization of the piRNA complex from rat testes ［J］. Science, 2006, 313(5785): 363-367.

［6］GRIVNA S T, BEYRET E, WANG Z, et al. A novel class of small RNAs in mouse spermatogenic cells ［J］. Genes Dev, 2006, 20(13): 1709-1714.

［7］WATANABE T, TAKEDA A, TSUKIYAMA T, et al. Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes ［J］. Genes Dev, 2006, 20(13): 1732-1743.

［8］HOUWING S, KAMMINGA L M, BEREZIKOV E, et al. A role for Piwi and piRNAs in germ cell maintenance and transposon silencing in Zebrafish ［J］. Cell, 2007, 129(1): 69-82.

［9］DORNER S, EULALIO A, HUNTZINGER E, et al. Delving into the diversity of silencing pathways-Symposium on MicroRNAs and siRNAs: Biological functions and mechanisms ［J］. EMBO Rep, 2007, 8(8): 723-729.

［10］KLATTENHOFF C, BRATU D P, MCGINNIS-SCHULTZ N, et al. Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response ［J］. Dev Cell, 2006, 12(1): 45-55.

［11］BRENNECKE J, ARAVIN A A, STARK A, et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila ［J］. Cell, 2007, 128(6): 1089-1103.

［12］LIM A K, KAI T. Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster ［J］. Proc Natl Acad Sci USA, 2007, 104(16): 6714-6719.

［13］BRENNECKE J, ARAVIN A A, STARK A, et al. Discrete small RNA generating loci as master regulators of transposon activity in Drosophila ［J］. Cell, 2007, 128(6): 1089-1103.

［14］ZAMORE P D. Somatic piRNA biogenesis ［J］. EMBO J, 2010, 29(19): 3219-3221.

［15］KIRINO Y, MOURELATOS Z. Mouse Piwiinteracting RNAs are 2'-O-methylated at their 3'termini ［J］. Nat Struct Mol Biol, 2007, 14(4): 347-348.

［16］OHARA T, SAKAGUCHI Y, SUZUKI T, et al. The 3'termini of mouse Piwi-interacting RNAs are 2'-O-methylated ［J］. Nat Struct Mol Biol, 2007, 14(4): 349-350.

［17］KLATTENHOFF C, THEURKAUF W. Biogenesis and germline functions of piRNAs ［J］. Development, 2008, 135(1): 3-9.

［18］KIRINO Y, KIM N, DE PLANELL-SAGUER M, et al. Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability ［J］. Nat Cell Biol, 2009, 11(5): 652-658.

［19］ARAVIN A A, VAN DER HEIJDEN G W, CASTANEDA J, et al. Cytoplasmic compartmentalization of the fetal piRNA pathway in mice ［J］. PLoS Genet, 2009, 5(12): 1-12.

［20］VAN DER HEIJDEN G W, CASTANEDA J, BORTVIN A. Bodies of evidence-compartmentalization of the piRNA pathway in mouse fetal prospermatogonia ［J］. Curr Opin Cell Biol, 2010, 22(6): 752-757.

［21］SHOJI M, TANAKA T, HOSOKAWA M, et al. The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline ［J］. Dev Cell, 2009, 17(6): 775-787.

［22］VAGIN V V, WOHLSCHLEGEL J, QU J, et al. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members ［J］. Genes Dev, 2009, 23(15): 1749-1762.

［23］KOJIMA K, KURAMOCHIMIYAGAWA S, CHUMA S, et al. Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cells ［J］. Genes Cells, 2009, 14(10): 1155-1165.

［24］GUNAWARDANE L S, SAITO K, NISHIDA K M, et al. A slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila ［J］. Science, 2007, 315(5818): 1587-1590.

［25］NISHIDA K M, SAITO K, MORI T, et al. Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad ［J］. RNA, 2007, 13(11): 1911-1922.

［26］SAITO K, NISHIDA K M, MORI T, et al. Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome ［J］. Genes Dev, 2006, 20(16): 2214-2222.

［27］BRENNECKE J, MALONE C D, ARAVIN A A, et al. An epigenetic role for maternally inherited piRNAs in transposon silencing ［J］. Science, 2008, 322(5906): 1387-1392.

［28］ARAVIN A A, SACHIDANANDAM R, GIRARD A, et al. Developmentally regulated piRNA clusters implicate MILI in transposon control ［J］. Science, 2007, 316(5825): 744-747.

［29］LI C J, VAGIN V V, LEE S H, et al. Collapse of germline piRNAs in the absence of argonaute3 reveals somatic piRNAs in flies ［J］. Cell, 2009, 137(3): 509-521.

［30］MALONE C D, BRENNECKE J, DUS M, et al. Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary ［J］. Cell, 2009, 137(3): 522-535.

［31］GHILDIYAL M, ZAMORE P D. Small silencing RNAs: An expanding universe ［J］. Nat Rev Genet, 2009, 10(2): 94-108.

［32］SAITO K, ISHIZU H, KOMAI M, et al. Roles for the Yb body components Armitage and Yb in primary piRNA biogenesis in Drosophila ［J］. Genes Dev, 2010, 24(22): 2493-2498.

［33］HAASE A D, FENOGLIO S, MUERDTER F, et al. Probing the initiation and effector phases of the somatic piRNA pathway in Drosophila ［J］. Genes Dev, 2010, 24(22): 2499-2504.

［34］OLIVIERI D, SYKORA M M, SACHIDANANDAM R, et al. An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila ［J］. EMBO J, 2010, 29(19): 3301-3317.

［35］KING F J, LIN H. Somatic signaling mediated by fs (1) Yb is essential for germline stem cell maintenance during Drosophila oogenesis ［J］. Development, 1999, 126(9): 1833-1844.

［36］KING F J, SZAKMARY A, COX D N, et al. Yb modulates the divisions of both germline and somatic stem cells through piwi- and hh-mediated mechanisms in the Drosophila ovary ［J］. Mol Cell, 2001, 7(3): 497-508.

［37］SZAKMARY A, REEDY M, QI H, et al. The Yb protein defines a novel organelle and regulates male germline stem cell self-renewal in Drosophila melanogaster ［J］. J Cell Biol, 2009, 185(4): 613-627.

［38］QI H Y, WATANABE T, KU H Y, et al. The Yb body, a major site for Piwi-associated RNA biogenesis and a gateway for Piwi expression and transport to the nucleus in somatic cells ［J］. J Biol Chem, 2010, 286(5): 3789-3797.

［39］SAITO K, INAGAKI S, MITUYAMA T, et al. A regulatory circuit for piwi by the large Maf gene traffic jam in Drosophila ［J］. Nature, 2009, 461(7268): 1296-1299.

［40］MURCHISON E P, KHERADPOUR P, SACHIDANANDAM R, et al. Conservation of small RNA pathways in platypus ［J］. Genome Res, 2008, 18(6):995-1004.

［41］KIRINO Y, MOURELATOS Z. Mouse Piwi-interacting RNAs are 2′-O-methylated at their 3′termini ［J］. Nat Struct Mol Biol, 2007, 14(4): 347-348.

［42］OHARA T, SAKAGUCHI Y, SUZUKI T, et al. The 3′termini of mouse Piwi-interacting RNAs are 2′-O-methylated ［J］. Nat Struct Mol Biol, 2007, 14(4): 349-350.

［43］HORWICH M D, LI C, MATRANGA C, et al. The Drosophila RNA methyltransferase, DmHen1, modifies germline piRNAs and single-stranded siRNAs in RISC ［J］. Curr Biol, 2007, 17(14): 1265-1272.

［44］SAITO K, SAKAGUCHI Y, SUZUKI T, et al. Pimet, the Drosophila homolog of HEN1, mediates 2′-O-methylation of Piwi-interacting RNAs at their 3′ends ［J］. Genes Dev, 2007, 21(13): 1603-1608.

［45］KAMMINGA L M, LUTEIJN M J, DEN BROEDER M J, et al. Hen1 is required for oocyte development and piRNA stability in zebrafish ［J］. EMBO J, 2010, 29(21): 3688-3700.

［46］KAWAOKA S, IZUMI N, KATSUMA S , et al. 3′ end formation of Piwi-interacting RNAs in vitro ［J］. Mol Cell, 2011, 43(6):1015-1022.

［47］NISHIDA K M, OKADA T N, KAWAMURA T, et al. Functional involvement of Tudor and dPRMT5 in the piRNA processing pathway in Drosophila germlines ［J］. EMBO J, 2009, 28(24): 3820-3831.

［48］CHEN C, JIN J, JAMES D A, et al. Mouse Piwi interactome identifies binding mechanism of Tdrkh Tudor domain to arginine methylated Miwi ［J］. Proc Natl Acad Sci USA, 2009, 106(48): 20336-20341.

［49］REUTER M, CHUMA S, TANAKA T, et al. Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile ［J］. Nat Struct Mol Biol, 2009, 16(6): 639-646.

［50］VAGIN V V, WOHLSCHLEGEL J, QU J, et al. Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members ［J］. Genes Dev, 2009, 23(15): 1749-1762.

［51］KURAMOCHI-MIYAGAWA S, WATANABE T, GOTOH K, et al. DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes ［J］. Genes Dev, 2008, 22(7): 908-917.

［52］KURAMOCHI-MIYAGAWA S, WATANABE T, GOTOH K, et al. MVH in piRNA processing and gene silencing of retrotransposons ［J］. Genes Dev, 2010, 24(9): 887-892.

［53］THOMSON T, LIN H F. The biogenesis and function of Piwi proteins and piRNAs: progress and prospect ［J］. Annu Rev Cell Dev Biol, 2009, 25: 355-376.

［54］DENG W, LIN H F. Miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for spermatogenesis ［J］. Dev Cell, 2002, 2(6): 819-830.

［55］ARAVIN A A, SACHIDANANDAM R, GIRARD A, et al. Developmentally regulated piRNA clusters implicate MILI in transposon control ［J］. Science, 2007, 316(5825): 744-747.

［56］CARMELL M A, GIRARD A, VAN DE KANT H J G, et al. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline ［J］. Dev Cell, 2007, 12(4): 503-514.

［57］WANG J Q, SAXE J P, TANAKA T, et al. Mili interacts with tudor domain-containing protein 1 in regulating spermatogenesis ［J］. Curr Biol, 2009, 19(8): 640-644.

［58］NISHIDA K M, SAITO K, MORI T, et al. Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad ［J］. RNA, 2007, 13(11): 1911-1922.

［59］ARAVIN A A, SACHIDANANDAM R, BOURC'HIS D, et al. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice ［J］. Mol Cell, 2008, 31(6): 785-799.

［60］SRIDHAR V V, KAPOOR A, ZHANG K L, et al. Control of DNA methylation and heterochromatic silencing by histone H2B deubiquitination ［J］. Nature, 2007, 447(7145): 735-738.

［61］LIM A K, TAO L H, KAI T. piRNAs mediate posttranscriptional retroelement silencing and localization to pi-bodies in the Drosophila germline ［J］. J Cell Biol, 2009, 186(3): 333-342.

［62］MA J B, YUAN Y R, MEISTER G, et al. Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein ［J］. Nature, 2005, 434(7033): 666-670.

［63］MA J B, YUAN Y R, MEISTER G, et al. Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex ［J］. Nature, 2005, 434(7033): 663-666.

［64］CHEN Y, PANE A, SCHUPBACH T. Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila ［J］. Curr Biol, 2007, 17(7): 637-642.

［65］PANE A, WEHR K, SCHUPBACH T. Zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline ［J］. Dev Cell, 2007, 12(6): 851-862.

［66］WATANABE T, CHUMA S, YAMAMOTO Y, et al. MITOPLD is a mitochondrial protein rssential for nuage formation and piRNA biogenesis in the mouse germline ［J］. Dev Cell, 2011, 20(3): 364-375.

［67］KLATTENHOFF C, XI H L, LI C J, et al. The Drosophila HP1 homolog rhino is required for transposon silencing and piRNA production by dual-strand clusters ［J］. Cell, 2009, 138(6): 1137-1149.

［68］ZHANG D P, DUARTEGUTERMAN P, LANGLOIS V S, et al. Temporal expression and steroidal regulation of piRNA pathway genes(mael, piwi, vasa) during Silurana (Xenopus) tropicalis embryogenesis and early larval development ［J］. Comp Biochem Physiol, Part C, 2010, 152(2): 202-206.

［69］MEIKAR O, DA ROS M, LILJENBACK H, et al. Accumulation of piRNAs in the chromatoid bodies purified by a novel isolation protocol ［J］. Exp Cell Res, 2010, 316(9): 1567-1575.

［70］LAKSHMI S S, AGRAWAL S. piRNABank: a web resource on classified and clustered Piwi-interacting RNAs ［J］. Nucleic Acids Res, 2008, 36(S1): D173-D177.

［71］JULIANOA C, STEELEB R, LINA H. Investigating piwi function in Hydra stem cells ［J］. Dev Biol, 2010, 344(1): 523.

［72］DIETZL G, CHEN D, SCHNORRER F, et al. A genomewide transgenic RNAi library for conditional gene inactivation in Drosophila ［J］. Nature, 2007, 448(7150): 151-156.

［73］WANG J B, CZECH B, CRUNK A, et al. Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles ［J］. Genome Res, 2011, 21(9): 1462-1477.

［74］GAN H Y, LIN X W, ZHANG Z Q, et al. piRNA profiling during specific stages of mouse spermatogenesis ［J］. RNA, 2011, 17(7): 1191-1203.

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