Endogenous RNA Interference is Driven by Copy Number

Overview

Journal Elife

Specialty Biology

Date 2014 Feb 13

PMID 24520161

Citations 14

Authors

Cristina Cruz

Jonathan Houseley

Affiliations

Soon will be listed here.

Abstract

A plethora of non-protein coding RNAs are produced throughout eukaryotic genomes, many of which are transcribed antisense to protein-coding genes and could potentially instigate RNA interference (RNAi) responses. Here we have used a synthetic RNAi system to show that gene copy number is a key factor controlling RNAi for transcripts from endogenous loci, since transcripts from multi-copy loci form double stranded RNA more efficiently than transcripts from equivalently expressed single-copy loci. Selectivity towards transcripts from high-copy DNA is therefore an emergent property of a minimal RNAi system. The ability of RNAi to selectively degrade transcripts from high-copy loci would allow suppression of newly emerging transposable elements, but such a surveillance system requires transcription. We show that low-level genome-wide pervasive transcription is sufficient to instigate RNAi, and propose that pervasive transcription is part of a defense mechanism capable of directing a sequence-independent RNAi response against transposable elements amplifying within the genome. DOI: http://dx.doi.org/10.7554/eLife.01581.001.

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References

Gantier M, Williams B . The response of mammalian cells to double-stranded RNA. Cytokine Growth Factor Rev. 2007; 18(5-6):363-71. PMC: 2084215. DOI: 10.1016/j.cytogfr.2007.06.016. View

Slotkin R, Martienssen R . Transposable elements and the epigenetic regulation of the genome. Nat Rev Genet. 2007; 8(4):272-85. DOI: 10.1038/nrg2072. View

Clark M, Amaral P, Schlesinger F, Dinger M, Taft R, Rinn J . The reality of pervasive transcription. PLoS Biol. 2011; 9(7):e1000625. PMC: 3134446. DOI: 10.1371/journal.pbio.1000625. View

Babiarz J, Ruby J, Wang Y, Bartel D, Blelloch R . Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev. 2008; 22(20):2773-85. PMC: 2569885. DOI: 10.1101/gad.1705308. View

Pryde F, Louis E . Limitations of silencing at native yeast telomeres. EMBO J. 1999; 18(9):2538-50. PMC: 1171335. DOI: 10.1093/emboj/18.9.2538. View

Hirota K, Miyoshi T, Kugou K, Hoffman C, Shibata T, Ohta K . Stepwise chromatin remodelling by a cascade of transcription initiation of non-coding RNAs. Nature. 2008; 456(7218):130-4. DOI: 10.1038/nature07348. View

Chekanova J, Gregory B, Reverdatto S, Chen H, Kumar R, Hooker T . Genome-wide high-resolution mapping of exosome substrates reveals hidden features in the Arabidopsis transcriptome. Cell. 2007; 131(7):1340-53. DOI: 10.1016/j.cell.2007.10.056. View

Goodman A, Daugharthy E, Kim J . Pervasive antisense transcription is evolutionarily conserved in budding yeast. Mol Biol Evol. 2012; 30(2):409-21. DOI: 10.1093/molbev/mss240. View

Redrup L, Branco M, Perdeaux E, Krueger C, Lewis A, Santos F . The long noncoding RNA Kcnq1ot1 organises a lineage-specific nuclear domain for epigenetic gene silencing. Development. 2009; 136(4):525-30. PMC: 2685953. DOI: 10.1242/dev.031328. View

10.

Nagano T, Mitchell J, Sanz L, Pauler F, Ferguson-Smith A, Feil R . The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science. 2008; 322(5908):1717-20. DOI: 10.1126/science.1163802. View

11.

Zhang H, Zhu J . RNA-directed DNA methylation. Curr Opin Plant Biol. 2011; 14(2):142-7. PMC: 3096526. DOI: 10.1016/j.pbi.2011.02.003. View

12.

Hobson D, Wei W, Steinmetz L, Svejstrup J . RNA polymerase II collision interrupts convergent transcription. Mol Cell. 2012; 48(3):365-74. PMC: 3504299. DOI: 10.1016/j.molcel.2012.08.027. View

13.

Pall G, Hamilton A . Improved northern blot method for enhanced detection of small RNA. Nat Protoc. 2008; 3(6):1077-84. DOI: 10.1038/nprot.2008.67. View

14.

Borsani O, Zhu J, Verslues P, Sunkar R, Zhu J . Endogenous siRNAs derived from a pair of natural cis-antisense transcripts regulate salt tolerance in Arabidopsis. Cell. 2005; 123(7):1279-91. PMC: 3137516. DOI: 10.1016/j.cell.2005.11.035. View

15.

Hainer S, Pruneski J, Mitchell R, Monteverde R, Martens J . Intergenic transcription causes repression by directing nucleosome assembly. Genes Dev. 2010; 25(1):29-40. PMC: 3012934. DOI: 10.1101/gad.1975011. View

16.

Drinnenberg I, Fink G, Bartel D . Compatibility with killer explains the rise of RNAi-deficient fungi. Science. 2011; 333(6049):1592. PMC: 3790311. DOI: 10.1126/science.1209575. View

17.

Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M . Antisense transcription in the mammalian transcriptome. Science. 2005; 309(5740):1564-6. DOI: 10.1126/science.1112009. View

18.

Nejepinska J, Malik R, Moravec M, Svoboda P . Deep sequencing reveals complex spurious transcription from transiently transfected plasmids. PLoS One. 2012; 7(8):e43283. PMC: 3420890. DOI: 10.1371/journal.pone.0043283. View

19.

Maillard P, Ciaudo C, Marchais A, Li Y, Jay F, Ding S . Antiviral RNA interference in mammalian cells. Science. 2013; 342(6155):235-8. PMC: 3853215. DOI: 10.1126/science.1241930. View

20.

Houseley J, Kotovic K, El Hage A, Tollervey D . Trf4 targets ncRNAs from telomeric and rDNA spacer regions and functions in rDNA copy number control. EMBO J. 2007; 26(24):4996-5006. PMC: 2080816. DOI: 10.1038/sj.emboj.7601921. View