Noncoding RNA. PiRNA-guided Transposon Cleavage Initiates Zucchini-dependent, Phased PiRNA Production

Overview

Journal Science

Specialty Science

Date 2015 May 16

PMID 25977554

Citations 214

Authors

Bo W Han

Wei Wang

Chengjian Li

Zhiping Weng

Phillip D Zamore

Affiliations

Soon will be listed here.

Abstract

PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing transposons. Primary piRNAs, generated from transcripts of genomic transposon "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the subsequent ~26 nt become the first in a series of phased primary piRNAs that bind Piwi, allowing piRNAs to spread beyond the site of RNA cleavage. The ping-pong pathway increases only the abundance of piRNAs, whereas production of phased primary piRNAs from cleaved transposon RNAs adds sequence diversity to the piRNA pool, allowing adaptation to changes in transposon sequence.

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References

Yoshikawa M, Peragine A, Park M, Poethig R . A pathway for the biogenesis of trans-acting siRNAs in Arabidopsis. Genes Dev. 2005; 19(18):2164-75. PMC: 1221887. DOI: 10.1101/gad.1352605. View

de Vanssay A, Bouge A, Boivin A, Hermant C, Teysset L, Delmarre V . Paramutation in Drosophila linked to emergence of a piRNA-producing locus. Nature. 2012; 490(7418):112-5. DOI: 10.1038/nature11416. View

Vagin V, Sigova A, Li C, Seitz H, Gvozdev V, Zamore P . A distinct small RNA pathway silences selfish genetic elements in the germline. Science. 2006; 313(5785):320-4. DOI: 10.1126/science.1129333. View

Gunawardane L, Saito K, Nishida K, Miyoshi K, Kawamura Y, Nagami T . A slicer-mediated mechanism for repeat-associated siRNA 5' end formation in Drosophila. Science. 2007; 315(5818):1587-90. DOI: 10.1126/science.1140494. View

Brennecke J, Aravin A, Stark A, Dus M, Kellis M, Sachidanandam R . Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. 2007; 128(6):1089-103. DOI: 10.1016/j.cell.2007.01.043. View

Pane A, Wehr K, Schupbach T . zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell. 2007; 12(6):851-62. PMC: 1945814. DOI: 10.1016/j.devcel.2007.03.022. View

Brennecke J, Malone C, Aravin A, Sachidanandam R, Stark A, Hannon G . An epigenetic role for maternally inherited piRNAs in transposon silencing. Science. 2008; 322(5906):1387-92. PMC: 2805124. DOI: 10.1126/science.1165171. View

Malone C, Brennecke J, Dus M, Stark A, McCombie W, Sachidanandam R . Specialized piRNA pathways act in germline and somatic tissues of the Drosophila ovary. Cell. 2009; 137(3):522-35. PMC: 2882632. DOI: 10.1016/j.cell.2009.03.040. View

Lau N, Robine N, Martin R, Chung W, Niki Y, Berezikov E . Abundant primary piRNAs, endo-siRNAs, and microRNAs in a Drosophila ovary cell line. Genome Res. 2009; 19(10):1776-85. PMC: 2765285. DOI: 10.1101/gr.094896.109. View

10.

Olivieri D, Sykora M, Sachidanandam R, Mechtler K, Brennecke J . An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila. EMBO J. 2010; 29(19):3301-17. PMC: 2957214. DOI: 10.1038/emboj.2010.212. View

11.

Zhang Z, Xu J, Koppetsch B, Wang J, Tipping C, Ma S . Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains. Mol Cell. 2011; 44(4):572-84. PMC: 3236501. DOI: 10.1016/j.molcel.2011.10.011. View

12.

Swarts D, Mosterd C, van Passel M, Brouns S . CRISPR interference directs strand specific spacer acquisition. PLoS One. 2012; 7(4):e35888. PMC: 3338789. DOI: 10.1371/journal.pone.0035888. View

13.

Lee H, Gu W, Shirayama M, Youngman E, Conte Jr D, Mello C . C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell. 2012; 150(1):78-87. PMC: 3410639. DOI: 10.1016/j.cell.2012.06.016. View

14.

Datsenko K, Pougach K, Tikhonov A, Wanner B, Severinov K, Semenova E . Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system. Nat Commun. 2012; 3:945. DOI: 10.1038/ncomms1937. View

15.

Bagijn M, Goldstein L, Sapetschnig A, Weick E, Bouasker S, Lehrbach N . Function, targets, and evolution of Caenorhabditis elegans piRNAs. Science. 2012; 337(6094):574-578. PMC: 3951736. DOI: 10.1126/science.1220952. View

16.

Ipsaro J, Haase A, Knott S, Joshua-Tor L, Hannon G . The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis. Nature. 2012; 491(7423):279-83. PMC: 3493678. DOI: 10.1038/nature11502. View

17.

Nishimasu H, Ishizu H, Saito K, Fukuhara S, Kamatani M, Bonnefond L . Structure and function of Zucchini endoribonuclease in piRNA biogenesis. Nature. 2012; 491(7423):284-7. DOI: 10.1038/nature11509. View

18.

Voigt F, Reuter M, Kasaruho A, Schulz E, Pillai R, Barabas O . Crystal structure of the primary piRNA biogenesis factor Zucchini reveals similarity to the bacterial PLD endonuclease Nuc. RNA. 2012; 18(12):2128-34. PMC: 3504665. DOI: 10.1261/rna.034967.112. View

19.

Xie Z, Allen E, Wilken A, Carrington J . DICER-LIKE 4 functions in trans-acting small interfering RNA biogenesis and vegetative phase change in Arabidopsis thaliana. Proc Natl Acad Sci U S A. 2005; 102(36):12984-9. PMC: 1200315. DOI: 10.1073/pnas.0506426102. View

20.

Sienski G, Donertas D, Brennecke J . Transcriptional silencing of transposons by Piwi and maelstrom and its impact on chromatin state and gene expression. Cell. 2012; 151(5):964-80. PMC: 3504300. DOI: 10.1016/j.cell.2012.10.040. View