MicroRNAs : New players in an old game

作者: M. Gupta , G. Brewer

DOI: 10.1073/PNAS.0601268103

关键词: P-bodiesCell biologyNonsense-mediated decayGene silencingmRNA surveillanceBiologyUntranslated regionGeneticsGene knockdownRNA silencingRNA interference

摘要: One of the cardinal steps in regulating gene expression is mRNA decay, and numerous pathways mechanisms that exist to regulate it underscore its importance. decay regulated by trans-acting factors assemble on cis-acting elements (1, 2). Together, they serve up- or down-regulate a given mRNA. Some levels involve surveillance such as nonsense-mediated (NMD) nonstop (NSD). The NMD pathway limits accumulation mRNAs contain premature termination codon whose translation would produce truncated protein. In NSD, do not because improper poly(A) site selection within coding region are rapidly degraded exosome, complex 3′→5′ exoribonucleases (3). Other recognition 3′ UTR sequences specific RNA-binding proteins. For example, AU-rich element (ARE)-mediated (AMD), binding ARE proteins initiates degradation 4). To one degree another, all these step-wise deconstruction involving trimming tail, process referred deadenylation; this followed removal 5′ m7GpppG cap both 5′→3′ body (5–7). This mechanism, first elucidated Saccharomyces cerevisiae, has been recognized for some time now. Another garnered much attention lately RNA interference (RNAi). First discovered Caenorhabditis elegans (8), RNAi now observed several other multicellular organisms, including mammals. triggered either small interfering (siRNA) or, cases, microRNA (miRNA) induces via endoribonucleolytic cleavage si/miRNA–mRNA annealing. siRNAs derive from sources double-stranded RNA, transposons, viruses perfectly complementary their targets (9–11). miRNAs ≈22 nt length encoded genomes plants animals. regions possessing imperfect complementarity UTRs subsets which anneal. leads translational silencing posttranscriptionally control (12). issue PNAS, Wu et al. (13) demonstrate miRNA can also promote rapid accelerating initial rate-limiting step, deadenylation.

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