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A multitasking Argonaute: exploring the many facets of C. elegans CSR-1

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Abstract

While initial studies of small RNA-mediated gene regulatory pathways focused on the cytoplasmic functions of such pathways, identifying roles for Argonaute/small RNA pathways in modulating chromatin and organizing the genome has become a topic of intense research in recent years. Nuclear regulatory mechanisms for Argonaute/small RNA pathways appear to be widespread, in organisms ranging from plants to fission yeast, Caenorhabditis elegans to humans. As the effectors of small RNA-mediated gene regulatory pathways, Argonaute proteins guide the chromatin-directed activities of these pathways. Of particular interest is the C. elegans Argonaute, chromosome segregation and RNAi deficient (CSR-1), which has been implicated in such diverse functions as organizing the holocentromeres of worm chromosomes, modulating germline chromatin, protecting the genome from foreign nucleic acid, regulating histone levels, executing RNAi, and inhibiting translation in conjunction with Pumilio proteins. CSR-1 interacts with small RNAs known as 22G-RNAs, which have complementarity to 25 % of the protein coding genes. This peculiar Argonaute is the only essential C. elegans Argonaute out of 24 family members in total. Here, we summarize the current understanding of CSR-1 functions in the worm, with emphasis on the chromatin-directed activities of this ever-intriguing Argonaute.

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Abbreviations

AGO:

Argonaute

CDE-1:

Co-suppression defective-1

CSR-1:

Chromosome segregation and RNAi deficient-1

ChIP:

Chromatin immunoprecipitation

Co-IP:

Co-immunoprecipitation

DRH-3:

Dicer-related helicase-3

dsRNA:

Double-stranded RNA

EKL-1:

Enhancer of KSR-1 lethality-1

EGO-1:

Enhancer of GLP-1

Eri:

Enhanced RNAi

FBF:

fem-3 mRNA binding factor

HCP-3/CENP-A:

Holocentromere protein 3/centromeric protein A

HRDE-1:

Heritable RNA deficient-1

HTZ-1/H2AZ:

Histone variant H2AZ homolog

ModENCODE:

Model organism encyclopedia of DNA elements

PAZ:

PIWI–Argonaute–Zwille

PIWI:

P-element induced wimpy testes

Rde:

RNAi deficient

RdRP:

RNA-dependent RNA polymerase

RNAi/exoRNAi:

Exogenous RNA interference

SAGO:

Secondary Argonaute

SLBP:

Stem loop binding protein

WAGO:

Worm Argonaute

References

  • Albertson DG, Thomson JN (1982) The kinetochores of Caenorhabditis elegans. Chromosoma 86:409–428

    Article  PubMed  CAS  Google Scholar 

  • Albertson DG, Rose AM, Villeneuve AM (1997) Chromosome organization, mitosis, and meiosis. C. elegans II. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  • Aoki K et al (2007) In vitro analyses of the production and activity of secondary small interfering RNAs in C. elegans. EMBO J 26:5007–5019

    Article  PubMed  CAS  Google Scholar 

  • Ashe A et al (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150:88–99

    Article  PubMed  CAS  Google Scholar 

  • Avgousti DC et al (2012) CSR-1 RNAi pathway positively regulates histone expression in C. elegans. EMBO J 31:3821–3832

    Article  PubMed  CAS  Google Scholar 

  • Bagijn MP et al (2012) Function, targets, and evolution of Caenorhabditis elegans piRNAs. Science 337:574–578

    Article  PubMed  CAS  Google Scholar 

  • Batista PJ et al (2008) PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans. Mol Cell 31:67–78

    Article  PubMed  CAS  Google Scholar 

  • Brodersen P, Voinnet O (2009) Revisiting the principles of microRNA target recognition and mode of action. Nat Rev Mol Cell Biol 10:141–148

    Article  PubMed  CAS  Google Scholar 

  • Buchwitz BJ et al (1999) A histone-H3-like protein in C. elegans. Nature 401:547–548

    Article  PubMed  CAS  Google Scholar 

  • Buck AH, Blaxter M (2013) Functional diversification of Argonautes in nematodes: an expanding universe. Biochem Soc Trans 41:881–886

    Article  PubMed  CAS  Google Scholar 

  • Buckley BA et al (2012) A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality. Nature 489:447–451

    Article  PubMed  CAS  Google Scholar 

  • Burton NO, Burkhart KB, Kennedy S (2011) Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans. Proc Natl Acad Sci U S A 108:19683–19688

    Article  PubMed  CAS  Google Scholar 

  • Chan FL et al (2012) Active transcription and essential role of RNA polymerase II at the centromere during mitosis. Proc Natl Acad Sci U S A 109:1979–1984

    Article  PubMed  CAS  Google Scholar 

  • Chu DS et al (2006) Sperm chromatin proteomics identifies evolutionarily conserved fertility factors. Nature 443:101–105

    Article  PubMed  CAS  Google Scholar 

  • Claycomb JM (2012) Caenorhabditis elegans small RNA pathways make their mark on chromatin. DNA Cell Biol 31(Suppl 1):S17–S33

    PubMed  Google Scholar 

  • Claycomb JM et al (2009) The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell 139:123–134

    Article  PubMed  CAS  Google Scholar 

  • Conine CC et al (2010) Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proc Natl Acad Sci U S A 107:3588–3593

    Article  PubMed  CAS  Google Scholar 

  • Corley SM, Gready JE (2008) Identification of the RGG box motif in Shadoo: RNA-binding and signaling roles? Bioinform Biol Insights 2:383–400

    PubMed  Google Scholar 

  • Dalzell JJ et al (2011) RNAi effector diversity in nematodes. PLoS Negl Trop Dis 5:e1176

    Article  PubMed  CAS  Google Scholar 

  • Das PP et al (2008) Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. Mol Cell 31:79–90

    Article  PubMed  CAS  Google Scholar 

  • Davila Lopez M, Samuelsson T (2008) Early evolution of histone mRNA 3′ end processing. RNA 14:1–10

    Article  PubMed  Google Scholar 

  • Dernburg AF (2001) Here, there, and everywhere: kinetochore function on holocentric chromosomes. J Cell Biol 153:F33–F38

    Article  PubMed  CAS  Google Scholar 

  • Duchaine TF et al (2006) Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell 124:343–354

    Article  PubMed  CAS  Google Scholar 

  • Fire A et al (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811

    Article  PubMed  CAS  Google Scholar 

  • Fischer SE (2010) Small RNA-mediated gene silencing pathways in C. elegans. Int J Biochem Cell Biol 42:1306–1315

    Article  PubMed  CAS  Google Scholar 

  • Friend K et al (2012) A conserved PUF-Ago-eEF1A complex attenuates translation elongation. Nat Struct Mol Biol 19:176–183

    Article  PubMed  CAS  Google Scholar 

  • Gassmann R et al (2012) An inverse relationship to germline transcription defines centromeric chromatin in C. elegans. Nature 484:534–537

    Article  PubMed  CAS  Google Scholar 

  • Gerstein MB et al (2010) Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 330:1775–1787

    Article  PubMed  CAS  Google Scholar 

  • Goday C, Pimpinelli S (1993) The occurrence, role and evolution of chromatin diminution in nematodes. Parasitol Today 9:319–322

    Article  PubMed  CAS  Google Scholar 

  • Grishok A (2013) Biology and mechanisms of short RNAs in Caenorhabditis elegans. Adv Genet 83:1–69

    Article  PubMed  CAS  Google Scholar 

  • Grishok A et al (2001) Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106:23–34

    Article  PubMed  CAS  Google Scholar 

  • Gu W et al (2009) Distinct argonaute-mediated 22G-RNA pathways direct genome surveillance in the C. elegans germline. Mol Cell 36:231–244

    Article  PubMed  CAS  Google Scholar 

  • Gu W et al (2012) CapSeq and CIP-TAP identify Pol II start sites and reveal capped small RNAs as C. elegans piRNA precursors. Cell 151:1488–1500

    Article  PubMed  CAS  Google Scholar 

  • Hall LE, Mitchell SE, O’Neill RJ (2012) Pericentric and centromeric transcription: a perfect balance required. Chromosome Res 20:535–546

    Article  PubMed  CAS  Google Scholar 

  • Hall SE et al (2013) RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans. RNA 19:306–319

    Article  PubMed  CAS  Google Scholar 

  • Han T et al (2009) 26G endo-siRNAs regulate spermatogenic and zygotic gene expression in Caenorhabditis elegans. Proc Natl Acad Sci U S A 106:18674–18679

    Article  PubMed  CAS  Google Scholar 

  • Hock J, Meister G (2008) The Argonaute protein family. Genome Biol 9:210

    Article  PubMed  Google Scholar 

  • Hutvagner G, Simard MJ (2008) Argonaute proteins: key players in RNA silencing. Nat Rev Mol Cell Biol 9:22–32

    Article  PubMed  CAS  Google Scholar 

  • Kataoka K, Mochizuki K (2011) Programmed DNA elimination in Tetrahymena: a small RNA-mediated genome surveillance mechanism. Adv Exp Med Biol 722:156–173

    Article  PubMed  CAS  Google Scholar 

  • Ketting RF (2011) The many faces of RNAi. Dev Cell 20:148–161

    Article  PubMed  CAS  Google Scholar 

  • Kim JK et al (2005) Functional genomic analysis of RNA interference in C. elegans. Science 308:1164–1167

    Article  PubMed  CAS  Google Scholar 

  • Kim VN, Han J, Siomi MC (2009) Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 10:126–139

    Article  PubMed  CAS  Google Scholar 

  • Kitagawa R (2009) Key players in chromosome segregation in Caenorhabditis elegans. Front Biosci 14:1529–1557

    Article  CAS  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  PubMed  CAS  Google Scholar 

  • Lee HC et al (2012) C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell 150:78–87

    Article  PubMed  CAS  Google Scholar 

  • Liu J et al (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441

    Article  PubMed  CAS  Google Scholar 

  • Luteijn MJ et al (2012) Extremely stable Piwi-induced gene silencing in Caenorhabditis elegans. EMBO J 31:3422–3430

    Article  PubMed  CAS  Google Scholar 

  • Maddox PS et al (2004) “Holo”er than thou: chromosome segregation and kinetochore function in C. elegans. Chromosome Res 12:641–653

    Article  PubMed  CAS  Google Scholar 

  • Maine EM (2010) Meiotic silencing in Caenorhabditis elegans. Int Rev Cell Mol Biol 282:91–134

    Article  PubMed  CAS  Google Scholar 

  • Maine EM et al (2005) EGO-1, a putative RNA-dependent RNA polymerase, is required for heterochromatin assembly on unpaired DNA during C. elegans meiosis. Curr Biol 15:1972–1978

    Article  PubMed  CAS  Google Scholar 

  • Makarova KS et al (2009) Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol Direct 4:29

    Article  PubMed  Google Scholar 

  • Maniar JM, Fire AZ (2011) EGO-1, a C. elegans RdRP, modulates gene expression via production of mRNA-templated short antisense RNAs. Curr Biol 21:449–459

    Article  PubMed  CAS  Google Scholar 

  • Marzluff WF, Wagner EJ, Duronio RJ (2008) Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail. Nat Rev Genet 9:843–854

    Article  PubMed  CAS  Google Scholar 

  • Melters DP et al (2012) Holocentric chromosomes: convergent evolution, meiotic adaptations, and genomic analysis. Chromosome Res 20:579–593

    Article  PubMed  CAS  Google Scholar 

  • Oegema K et al (2001) Functional analysis of kinetochore assembly in Caenorhabditis elegans. J Cell Biol 153:1209–1226

    Article  PubMed  CAS  Google Scholar 

  • Pak J, Fire A (2007) Distinct populations of primary and secondary effectors during RNAi in C. elegans. Science 315:241–244

    Article  PubMed  CAS  Google Scholar 

  • Robert VJ et al (2005) Chromatin and RNAi factors protect the C. elegans germline against repetitive sequences. Genes Dev 19:782–787

    Article  PubMed  CAS  Google Scholar 

  • Rocheleau CE et al (2008) The Caenorhabditis elegans ekl (enhancer of ksr-1 lethality) genes include putative components of a germline small RNA pathway. Genetics 178:1431–1443

    Article  PubMed  CAS  Google Scholar 

  • She X et al (2009) Regulation of heterochromatin assembly on unpaired chromosomes during Caenorhabditis elegans meiosis by components of a small RNA-mediated pathway. PLoS Genet 5:e1000624

    Article  PubMed  Google Scholar 

  • Shi Z et al (2013) High-throughput sequencing reveals extraordinary fluidity of miRNA, piRNA, and siRNA pathways in nematodes. Genome Res 23:497–508

    Article  PubMed  CAS  Google Scholar 

  • Shirayama M et al (2012) piRNAs initiate an epigenetic memory of nonself RNA in the C. elegans Germline. Cell 150:65–77

    Article  PubMed  CAS  Google Scholar 

  • Smardon A et al (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10:169–178

    Article  PubMed  CAS  Google Scholar 

  • Song JJ et al (2004) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437

    Article  PubMed  CAS  Google Scholar 

  • Spike CA et al (2008) DEPS-1 promotes P-granule assembly and RNA interference in C. elegans germ cells. Development 135:983–993

    Article  PubMed  CAS  Google Scholar 

  • Stimpson KM, Sullivan BA (2011) Histone H3K4 methylation keeps centromeres open for business. EMBO J 30:233–234

    Article  PubMed  CAS  Google Scholar 

  • Sullivan BA, Karpen GH (2004) Centromeric chromatin exhibits a histone modification pattern that is distinct from both euchromatin and heterochromatin. Nat Struct Mol Biol 11:1076–1083

    Article  PubMed  CAS  Google Scholar 

  • Tabara H et al (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99:123–132

    Article  PubMed  CAS  Google Scholar 

  • Updike DL, Strome S (2009) A genomewide RNAi screen for genes that affect the stability, distribution and function of P granules in Caenorhabditis elegans. Genetics 183:1397–1419

    Article  PubMed  CAS  Google Scholar 

  • Updike D, Strome S (2010) P granule assembly and function in Caenorhabditis elegans germ cells. J Androl 31:53–60

    Article  PubMed  CAS  Google Scholar 

  • Vagin VV et al (2009) Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev 23:1749–1762

    Article  PubMed  CAS  Google Scholar 

  • van Wolfswinkel JC, Ketting RF (2010) The role of small non-coding RNAs in genome stability and chromatin organization. J Cell Sci 123:1825–1839

    Article  PubMed  Google Scholar 

  • van Wolfswinkel JC et al (2009) CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs. Cell 139:135–148

    Article  PubMed  Google Scholar 

  • Vasale JJ et al (2010) Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway. Proc Natl Acad Sci U S A 107:3582–3587

    Article  PubMed  CAS  Google Scholar 

  • Vought VE et al (2005) EGO-1, a putative RNA-directed RNA polymerase, promotes germline proliferation in parallel with GLP-1/notch signaling and regulates the spatial organization of nuclear pore complexes and germline P granules in Caenorhabditis elegans. Genetics 170:1121–1132

    Article  PubMed  CAS  Google Scholar 

  • Wang J et al (2011) Deep small RNA sequencing from the nematode Ascaris reveals conservation, functional diversification, and novel developmental profiles. Genome Res 21:1462–1477

    Article  PubMed  CAS  Google Scholar 

  • Wang J et al (2012) Silencing of germline-expressed genes by DNA elimination in somatic cells. Dev Cell 23:1072–1080

    Article  PubMed  CAS  Google Scholar 

  • Yigit E et al (2006) Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell 127:747–757

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We are grateful to Michelle Francisco and other members of the Claycomb lab as well as Dr. Andrew Spence for insightful discussions regarding the many functions of our favorite Argonaute, CSR-1. J.M.C. is The Canada Research Chair in Small RNA Biology. C.J.W. was supported by a CIHR Banting and Best Master’s Fellowship. M.W. was supported by an Ontario Graduate Scholarship. Research in the Claycomb lab is supported by CIHR Grants MOP-274660, and CAP-262134, and NSERC Grant RGPIN-418.

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Authors and Affiliations

  1. Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada

    Christopher J. Wedeles, Monica Z. Wu & Julie M. Claycomb

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  1. Christopher J. Wedeles
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  2. Monica Z. Wu
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  3. Julie M. Claycomb
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Correspondence to Julie M. Claycomb.

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Responsible Editors: Brian P. Chadwick, Kristin C. Scott, and Beth A. Sullivan.

C. J. Wedeles and M. Z. Wu contributed equally.

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Wedeles, C.J., Wu, M.Z. & Claycomb, J.M. A multitasking Argonaute: exploring the many facets of C. elegans CSR-1. Chromosome Res 21, 573–586 (2013). https://doi.org/10.1007/s10577-013-9383-7

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