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  • Review Article
  • Published:

Small non-coding RNAs in animal development

Nature Reviews Molecular Cell Biology volume 9, pages 219–230 (2008)Cite this article

Key Points

  • The functional roles of small non-coding RNAs in vertebrates are beginning to be elucidated thanks to specific gene-deletion approaches.

  • miR-15, miR-16 and miR-430 are involved in modulation of the Nodal signalling pathway in different phases of vertebrate embryonic development.

  • miR-124 contributes to the adoption of neural cell fate by regulating the switch between PTB and nPTB, two regulators of alternative splicing.

  • miR-208 deletion results in a failure to produce cardiac hypertrophy in response to various stresses.

  • miR-181 and miR-155 have a complex regulatory role in lymphocyte maturation and the immune response.

  • piRNAs are a novel class of small non-coding RNAs that are expressed in the germline, and that are possibly involved in inhibiting the mobilization of transposons.

Abstract

The modulation of gene expression by small non-coding RNAs is a recently discovered level of gene regulation in animals and plants. In particular, microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs) have been implicated in various aspects of animal development, such as neuronal, muscle and germline development. During the past year, an improved understanding of the biological functions of small non-coding RNAs has been fostered by the analysis of genetic deletions of individual miRNAs in mammals. These studies show that miRNAs are key regulators of animal development and are potential human disease loci.

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Figure 1: MicroRNAs in neuronal development.
Figure 2: MicroRNAs in cardiac development.
Figure 3: Role of miR-181 and miR-155 in lymphocyte development.

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Acknowledgements

We thank M. Boehm for critical reading of the manuscript. G.S. was supported by the Anna Fuller Fund and a Sessel Postdoctoral Fellowship. F.S. was supported by grants from the National Institutes of Health, the McDonnell Foundation and the Ellison Medical Foundation.

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  1. Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, 06520, Connecticut, USA

    Giovanni Stefani & Frank J. Slack

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Glossary

Piwi-interacting RNAs

(piRNAs). Short RNA molecules (24–30 nt long) that are processed in a Dicer- and Drosha-independent manner. They associate with Piwi proteins and have a role in transposon silencing in flies. In mammals, they are restricted mostly to male germ cells.

RNase III

One of a highly conserved family of endoribonucleases that cleave double-stranded RNA and have an important role in the maturation of ribosomal RNA, among other processes.

miRNA-induced silencing complex

(miRISC). A multicomponent gene regulatory complex that is activated by a microRNA (miRNA) associated with an Argonaute protein and that regulates gene expression, mediated by the sequence complementarity between the miRNA and the target mRNA.

Argonaute protein

One of a family of evolutionarily conserved proteins that are characterized by the presence of two homology domains (PAZ and PIWI). Argonaute proteins are essential for diverse RNA-silencing pathways.

P bodies

Cytoplasmic foci that are thought to store and degrade translationally repressed RNA.

Hyperplasia

Enlargement of an organ resulting from an increased number of its cells.

Deep sequencing techniques

Sequencing to high coverage, where coverage (or depth) corresponds to the average number of times that a nucleotide is sequenced.

Small interfering RNA

(siRNA). Short double-stranded RNA molecules (∼21–23 nt) that guide the cleavage and degradation of RNA that is complementary to one of its strands.

Germ-line stem cells

(GSCs). Cells that have the ability to self-renew and to generate differentiated cells that are restricted to the germ cell lineage.

Primordial germ cells

Embryonic cells that give rise to the germ cell lineage.

rasiRNA

Repeat-associated small interfering RNA that is derived from highly repetitive genomic loci. rasiRNA is involved in the establishment and maintenance of heterochromatin and transposon control.

Seminiferous tubules

Structures in the testis where spermatocytes mature.

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Stefani, G., Slack, F. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 9, 219–230 (2008). https://doi.org/10.1038/nrm2347

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