Small silencing RNAs: an expanding universe

• Published in: Nature reviews. Genetics Vol. 10; no. 2; pp. 94 - 108
• Main Authors: Zamore, Phillip D, Ghildiyal, Megha
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2009; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Cancer Research; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - genetics; Gene Function; Gene silencing; Genes; Genetic regulation; Human Genetics; Infections; Insects; MicroRNAs; MicroRNAs - genetics; Models, Genetic; Molecular and cellular biology; Molecular genetics; Nematodes; Physiological aspects; Proteins; review-article; RNA; RNA Interference; RNA polymerase; RNA, Small Interfering - genetics; RNA-Induced Silencing Complex - genetics; Specialization; Transcription. Transcription factor. Splicing. Rna processing; Viral infections; United States; Gene silencing; Regulation(control); Double stranded RNA; RNA interference; Micro RNA; piRNA; siRNA; Review; Biogenesis
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg2504

Key Points 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. 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. Small interfering RNAs are typically 21 nucleotides and they are derived from dsRNA, the nearly universal eukaryotic signal for 'foreignness'. 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. 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. Piwi-interacting RNAs participate in a feed-forward amplification loop that monitors and silences transposon expression in the germ line. Small RNA pathways, although distinct, share protein components and repress and enhance each other. Such 'cross talk' between small RNA pathways is poorly understood. Small RNAs — including miRNAs, siRNAs and piRNAs — differ in their biogenesis, modes of target regulation and biological functions. There are also interconnections between these pathways, which compete and collaborate in some of their regulatory and protective roles. 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.