RNAi triggered by specialized machinery silences developmental genes and retrotransposons

Soichiro Yamanaka, Sameet Mehta, Francisca E. Reyes-Turcu, Fanglei Zhuang, Ryan T. Fuchs, Yikang Rong, Gregory B. Robb, Shiv I S Grewal

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

RNA interference (RNAi) is a conserved mechanism in which small interfering RNAs (siRNAs) guide the degradation of cognate RNAs, but also promote heterochromatin assembly at repetitive DNA elements such as centromeric repeats. However, the full extent of RNAi functions and its endogenous targets have not been explored. Here we show that, in the fission yeast Schizosaccharomyces pombe, RNAi and heterochromatin factors cooperate to silence diverse loci, including sexual differentiation genes, genes encoding transmembrane proteins, and retrotransposons that are also targeted by the exosome RNA degradation machinery. In the absence of the exosome, transcripts are processed preferentially by the RNAi machinery, revealing siRNA clusters and a corresponding increase in heterochromatin modifications across large domains containing genes and retrotransposons. We show that the generation of siRNAs and heterochromatin assembly by RNAi is triggered by a mechanism involving the canonical poly(A) polymerase Pla1 and an associated RNA surveillance factor Red1, which also activate the exosome. Notably, siRNA production and heterochromatin modifications at these target loci are regulated by environmental growth conditions, and by developmental signals that induce gene expression during sexual differentiation. Our analyses uncover an interaction between RNAi and the exosome that is conserved in Drosophila, and show that differentiation signals modulate RNAi silencing to regulate developmental genes.

Original languageEnglish
Pages (from-to)557-560
Number of pages4
JournalNature
Volume493
Issue number7433
DOIs
Publication statusPublished - 2013 Jan 24
Externally publishedYes

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Developmental Genes
Retroelements
RNA Interference
Heterochromatin
Exosomes
Small Interfering RNA
Sex Differentiation
Schizosaccharomyces
RNA Stability
Exosome Multienzyme Ribonuclease Complex
Polynucleotide Adenylyltransferase
RNA
Genes
Drosophila
Gene Expression
DNA

ASJC Scopus subject areas

  • General

Cite this

Yamanaka, S., Mehta, S., Reyes-Turcu, F. E., Zhuang, F., Fuchs, R. T., Rong, Y., ... Grewal, S. I. S. (2013). RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Nature, 493(7433), 557-560. https://doi.org/10.1038/nature11716

RNAi triggered by specialized machinery silences developmental genes and retrotransposons. / Yamanaka, Soichiro; Mehta, Sameet; Reyes-Turcu, Francisca E.; Zhuang, Fanglei; Fuchs, Ryan T.; Rong, Yikang; Robb, Gregory B.; Grewal, Shiv I S.

In: Nature, Vol. 493, No. 7433, 24.01.2013, p. 557-560.

Research output: Contribution to journalArticle

Yamanaka, S, Mehta, S, Reyes-Turcu, FE, Zhuang, F, Fuchs, RT, Rong, Y, Robb, GB & Grewal, SIS 2013, 'RNAi triggered by specialized machinery silences developmental genes and retrotransposons', Nature, vol. 493, no. 7433, pp. 557-560. https://doi.org/10.1038/nature11716
Yamanaka S, Mehta S, Reyes-Turcu FE, Zhuang F, Fuchs RT, Rong Y et al. RNAi triggered by specialized machinery silences developmental genes and retrotransposons. Nature. 2013 Jan 24;493(7433):557-560. https://doi.org/10.1038/nature11716
Yamanaka, Soichiro ; Mehta, Sameet ; Reyes-Turcu, Francisca E. ; Zhuang, Fanglei ; Fuchs, Ryan T. ; Rong, Yikang ; Robb, Gregory B. ; Grewal, Shiv I S. / RNAi triggered by specialized machinery silences developmental genes and retrotransposons. In: Nature. 2013 ; Vol. 493, No. 7433. pp. 557-560.
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