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19 The Biology of Short RNAs

Christian P. Petersen, John G. Doench, Alla Grishok, Phillip A. Sharp


The RNA World is commonly discussed in the context of RNA catalysis. During this ancient stage of biology, however—where the genetic material consisted of RNA and many processes were catalyzed by RNA—RNA was almost certainly also the major regulatory molecule controlling both the flow of information and the rate of catalytic processes. Elsewhere in this volume, RNA is described as regulating many common processes such as translation, RNA splicing, and protein functions. These regulatory interactions use a combination of RNA features—primary sequence, secondary and tertiary structure—for recognition of other components for regulation.

Given the complexity of known RNA molecules involved in regulation, it was a major surprise when simple RNAs of only about 22 nucleotides in length were found to have many general functions in the regulation of biological systems. These short RNAs are derived from double-stranded RNA (dsRNA) precursors, are recognized by multicomponent machinery in cells, and direct the regulation of gene expression through their primary sequence. The discovery of these RNA interference (RNAi)-related processes have radically changed concepts about the nature of regulatory factors in organisms. In theory, any linear sequence of RNA can be converted into a trans-acting regulatory factor by small RNA regulatory mechanisms. Small RNAs are now known to regulate expression of information in DNA sequences at the level of mRNA stability, mRNA translation, and transcription of RNA. Although it is possible that these processes utilizing short RNAs had their origins in the RNA World, it seems more likely that these...

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