Review

RNA-mediated epigenetic regulation of gene expression

Published online:

Abstract

Diverse classes of RNA, ranging from small to long non-coding RNAs, have emerged as key regulators of gene expression, genome stability and defence against foreign genetic elements. Small RNAs modify chromatin structure and silence transcription by guiding Argonaute-containing complexes to complementary nascent RNA scaffolds and then mediating the recruitment of histone and DNA methyltransferases. In addition, recent advances suggest that chromatin-associated long non-coding RNA scaffolds also recruit chromatin-modifying complexes independently of small RNAs. These co-transcriptional silencing mechanisms form powerful RNA surveillance systems that detect and silence inappropriate transcription events, and provide a memory of these events via self-reinforcing epigenetic loops.

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Acknowledgements

D.H. was supported by the US National Science Foundation Graduate Research Fellowship Program. Research in D.M.'s laboratory is supported by grants from the US National Institutes of Health. D.M. is an Investigator of the Howard Hughes Medical Institute.

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Affiliations

  1. Howard Hughes Medical Institute, Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.

    • Daniel Holoch
    •  & Danesh Moazed

Authors

  1. Search for Daniel Holoch in:

  2. Search for Danesh Moazed in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Danesh Moazed.

Supplementary information

PDF files

  1. 1.

    Supplementary information S1 (figure)

    Conservation and divergence of RNA silencing pathways.

Glossary

RNA interference

(RNAi). Broadly refers to RNA silencing pathways that use Argonaute and PIWI proteins and small RNAs to silence gene expression.

Small interfering RNAs

(siRNAs). 22–24-nucleotide small RNAs that are generated from longer double-stranded RNA precursors by the ribonuclease Dicer.

Heterochromatin

Regions of chromatin that retain the condensed appearance of mitotic chromosomes throughout the cell cycle. Heterochromatic regions are associated with repressive histone modifications and structural proteins, and are transcriptionally silent.

Argonaute

(AGO). A family of proteins that bind to small RNAs and that are conserved in all domains of life. They mediate target recognition via base-pairing interactions between their bound small RNA and complementary coding or non-coding RNAs.

Heterochromatic gene silencing

Silencing of gene expression within heterochromatin. It was originally thought to exclusively involve transcriptional gene silencing mechanisms, but recent findings indicate that co-transcriptional degradation of nascent RNA, or co-transcriptional gene silencing, also play important parts in silencing.

Pericentromeric DNA repeat

A repeated DNA sequence that surrounds the centromeres of most eukaryotic chromosomes. These repeats are assembled into heterochromatin, which has been demonstrated to have roles in cohesin recruitment in fission yeast and mammals, and de novo centromere assembly in fission yeast.

RNA-induced transcriptional silencing

(RITS). A protein complex first identified in Schizosaccharomyces pombe. In addition to Argonaute 1, the RITS complex contains a GW domain protein, Tas3, and a chromodomain protein, Chp1, which tether the complex to the chromosome via interactions with nascent long non-coding RNAs and nucleosomes with methylated histone H3 lysine 9.

Long terminal repeat

(LTR). A DNA sequence that is repeated at the ends of retrotransposons or pro-viral DNA that is formed from retroviral RNA by reverse transcription. Plant and mammalian genomes contain thousands of LTRs.

Epigenetic phenomena

Phenomena in which changes in gene expression occur without a corresponding change in the DNA sequence; such changes are stable in the absence of initiating signals.

Paramutation

The ability of a silent allele to convert an active allele to the silent (and paramutagenic) form. It was first described in Zea mays.