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The rise of regulatory RNA

Abstract

Discoveries over the past decade portend a paradigm shift in molecular biology. Evidence suggests that RNA is not only functional as a messenger between DNA and protein but also involved in the regulation of genome organization and gene expression, which is increasingly elaborate in complex organisms. Regulatory RNA seems to operate at many levels; in particular, it plays an important part in the epigenetic processes that control differentiation and development. These discoveries suggest a central role for RNA in human evolution and ontogeny. Here, we review the emergence of the previously unsuspected world of regulatory RNA from a historical perspective.

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Figure 1
Figure 2: Complex expression of the genome and examples of non-coding RNA expression.
Figure 3: Functional pathways of small regulatory RNAs.
Figure 4: Various roles for long non-coding RNAs in cellular regulation.

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Acknowledgements

This work was supported by the US National Institutes of Health grant PO1 AI099783-01 and the Australian Research Council Future Fellowship FT130100572 to K.V.M., and by the National Health and Medical Research Council Australia Fellowship 631688 to J.S.M.

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Glossary

Antisense RNA

A single-stranded RNA that is complementary to an mRNA or a gene.

Encyclopedia of DNA Elements

(ENCODE). An international consortium involved in building a comprehensive list of functional elements in the human genome.

Heterogeneous nuclear RNA

(hnRNA). A type of RNA that is similar to mRNA or pre-mRNA but that is retained predominantly in the nucleus.

Introns

A term first coined by Gilbert to describe the RNA regions that are removed, by being spliced out, to produce mRNAs.

PIWI-interacting RNAs

(piRNAs). Small RNAs that are associated with the PIWI protein complex and that emanated from transposon-like elements

RNA CaptureSeq

A method that combines the ability to capture RNA (that is, to isolate and enrich for certain types of RNA) with deep sequencing technology to mine the human transcriptome.

RNA-directed DNA methylation

An epigenetic process whereby processed double-stranded small (21–24-nucleotide) RNAs guide the methylation of homologous DNA loci.

Small interfering RNAs

(siRNAs). Small interfering, double-stranded RNAs that can be used to suppress homology-containing transcripts in a transcriptional and post-transcriptional manner.

Splice site RNAs

(spliRNAs). Small RNAs that are derived from the 3′ ends of exons adjacent to splice sites and that are similar to transcription initiation RNAs (tiRNAs).

Transcriptional gene silencing

The regulation of a gene at the transcriptional level, in contrast to post-transcriptional gene silencing, in which silencing of gene expression occurs at the mRNA or translational level, after transcription has occurred.

Transcription initiation RNAs

(tiRNAs). Small RNAs associated with promoters with peak density at ~ 15–35 nucleotides downstream of transcription start sites.

Transinduction

A genetic phenomenon whereby mRNA transcription induces transcription of nearby enhancers and intergenic non-coding RNAs.

Transposons

Mobile genetic elements with evolutionary links to retroviruses.

Transvection

A genetic phenomenon whereby non-coding regions can induce transcription of coding regions on other chromosomes.

Untranslated regions

(UTRs). Sequences either side of a coding sequence on a strand of mRNA; these can be 5′ leader sequences or 3′ trailer sequences.

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Morris, K., Mattick, J. The rise of regulatory RNA. Nat Rev Genet 15, 423–437 (2014). https://doi.org/10.1038/nrg3722

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