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Conserved chromosomal functions of RNA interference

Nature Reviews Genetics volume 21, pages 311–331 (2020)Cite this article

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Abstract

RNA interference (RNAi), a cellular process through which small RNAs target and regulate complementary RNA transcripts, has well-characterized roles in post-transcriptional gene regulation and transposon repression. Recent studies have revealed additional conserved roles for RNAi proteins, such as Argonaute and Dicer, in chromosome function. By guiding chromatin modification, RNAi components promote chromosome segregation during both mitosis and meiosis and regulate chromosomal and genomic dosage response. Small RNAs and the RNAi machinery also participate in the resolution of DNA damage. Interestingly, many of these lesser-studied functions seem to be more strongly conserved across eukaryotes than are well-characterized functions such as the processing of microRNAs. These findings have implications for the evolution of RNAi since the last eukaryotic common ancestor, and they provide a more complete view of the functions of RNAi.

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Fig. 1: Small-RNA biogenesis pathways and the evolutionary conservation of their components.
Fig. 2: Chromosome segregation phenotypes of RNAi are highly conserved.
Fig. 3: Faithful chromosome segregation is ensured by the recruitment and protection of centromeric cohesin.
Fig. 4: RNAi regulates dosage at the transcript, chromatin and DNA levels.
Fig. 5: Roles of RNAi in the recognition and resolution of DNA damage.

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Acknowledgements

The authors thank B. Roche for critical input and other members of the Martienssen Lab for helpful discussions. Research in the Martienssen laboratory is supported by the Howard Hughes Medical Institute and the National Institutes of Health (GM076396).

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  1. Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

    Michael J. Gutbrod & Robert A. Martienssen

  2. Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

    Robert A. Martienssen

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  1. Michael J. Gutbrod
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The authors contributed equally to all aspects of the article.

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Glossary

microRNAs

(miRNAs). Short, non-coding RNAs derived from hairpin structures that target mRNAs for cleavage and/or degradation in post-transcriptional gene silencing.

Small interfering RNAs

(siRNAs). Short, non-coding RNAs derived from longer double-stranded RNA molecules that target complementary RNAs in repressive mechanisms.

Last eukaryotic common ancestor

(LECA). The most evolutionarily recent ancestral eukaryotic cell that gave rise to all modern eukaryotic organisms.

Co-transcriptional gene silencing

(CTGS). A mechanism of targeting nascent RNA molecules produced by an RNA polymerase for the formation of repressive epigenetic modifications at the transcribed loci.

Cohesin

A large multi-subunit protein complex that participates in a variety of processes, including sister chromatid separation during cell division, the attachment of spindles to chromosomes and the repair of DNA damage through recombination.

Chromosome bridging

The abnormal formation of a continuous piece of DNA between the two new daughter nuclei in late anaphase, caused by a number of mechanisms that prevent the separation of sister chromatids or the migration of chromatids to the new nuclei.

Chicken DT40 cell line

A lymphoma-derived cell line that is widely used, owing to its high levels of homologous recombination. It can also be transformed with whole chromosomes by microcell fusion to achieve chromosomal hybrids.

Apospory

The production of gametophytes directly from diploid sporophytes, without meiosis.

Polyploidy

A genomic state defined by having more than two (in the case of diploid organisms) homologous sets of chromosomes.

Synthetic lethality

A genetic relationship in which the combination of mutations in two genes is highly deleterious, whereas each individual mutation is not.

Ribosomal DNA

(rDNA). A tandemly repeated genomic locus that encodes rRNA and leads to the production of ribosomes.

Recombination

The linking of DNA segments to form a new molecule; it can be used in DNA damage repair in a process called homologous recombination (HR), in which sequences are exchanged between similar stretches of DNA.

Nucleoli

A dense nuclear structure, composed primarily of rDNA, that is the site of ribosome biogenesis.

Double-strand breaks

(DSBs). A form of DNA damage in which the covalent bonds of the DNA double helix are severed at the same locus; this lesion is repaired through either HR or the less precise mechanism of non-homologous end joining, depending on a number of factors.

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Gutbrod, M.J., Martienssen, R.A. Conserved chromosomal functions of RNA interference. Nat Rev Genet 21, 311–331 (2020). https://doi.org/10.1038/s41576-019-0203-6

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