Key Points
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Like nearly all biological mechanisms, small RNA-directed pathways are both elegantly simple — small RNA guides use sequence complementarity to identify their targets — and shockingly complex, with myriad proteins required to excise small RNA guides from much longer precursors and still more required to carry out small RNA-directed functions.
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Despite this complexity, the defining features of small silencing RNAs are their short length (∼20–30 nucleotides) and their association with members of the Argonaute family of proteins.
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Small interfering RNAs are typically 21 nucleotides and they are derived from dsRNA, the nearly universal eukaryotic signal for 'foreignness'.
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Small interfering RNAs can be both exogenous and endogenous in origin in plants and animals, and provide an epigenetic component of resistance against biotic and abiotic stress.
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MicroRNAs 'tune' and regulate development and many other biological processes in plants and animals. MicroRNAs are encoded in the genome and typically repress their mRNA targets by partial base-pairing, and hence have the potential to regulate many distinct mRNA targets.
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Piwi-interacting RNAs participate in a feed-forward amplification loop that monitors and silences transposon expression in the germ line.
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Small RNA pathways, although distinct, share protein components and repress and enhance each other. Such 'cross talk' between small RNA pathways is poorly understood.
Abstract
Since the discovery in 1993 of the first small silencing RNA, a dizzying number of small RNA classes have been identified, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). These classes differ in their biogenesis, their modes of target regulation and in the biological pathways they regulate. There is a growing realization that, despite their differences, these distinct small RNA pathways are interconnected, and that small RNA pathways compete and collaborate as they regulate genes and protect the genome from external and internal threats.
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Acknowledgements
We thank H. Seitz for bioinformatic assistance and X. Chen, I. Pekker and S. Ameres for helpful discussions. This work was supported, in part, by grants from the National Institutes of Health to P.D.Z. (GM065236 and GM062862).
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Glossary
- Argonaute
-
Argonaute proteins are the effectors of small RNA-directed silencing. Small RNAs guide Argonautes to their RNA targets; Argonautes carry out the regulation. Argonaute proteins are characterized by two domains — Piwi (a ribonuclease domain) and PAZ (a ssRNA-binding module).
- Retrotransposon
-
A transposable element that replicates via an RNA intermediate, which is converted by reverse transcriptase to cDNA. The cDNA can be inserted into genomic DNA, increasing the number of copies of the retrotransposon in the genome.
- Sequencing depth
-
The number of sequences obtained by high-throughput sequencing for a specific sample. Sequencing depth is often expressed as 'genome-matching reads'.
- Pachytene
-
Pachytene is the stage of meiotic prophase during which the homologous chromosomes condense and separate into two chromatids. At the pachytene stage, homologous chromosomes pair and crossing over — the exchange of DNA segments — occurs between two non-sister chromatids.
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Ghildiyal, M., Zamore, P. Small silencing RNAs: an expanding universe. Nat Rev Genet 10, 94–108 (2009). https://doi.org/10.1038/nrg2504
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DOI: https://doi.org/10.1038/nrg2504
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