Interrelationships of the Pathways of mRNA Decay and Translation in Eukaryotic Cells

来自 NCBI

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摘要：

While the potential importance of stability to the regulation of gene expression has been recognized, the structures and mechanisms involved in the determination of individual decay rates have just begun to be elucidated, particularly in mammalian systems and . It is now well established that decay is not a default process, in which an array of nonspecific nucleases degrades indiscriminately based on target size or protection of the substrate. Rather, like , , and , decay is a precise process dependent on a variety of specific -acting sequences and trans-acting factors. Entry into the pathways of decay is triggered by at least three types of initiating event: poly(A) shortening, arrest of at a premature nonsense codon, and endonucleolytic cleavage. Steps subsequent to poly(A) shortening or premature converge in a pathway that progresses from removal of the 5' cap to exonucleolytic of the body of the . fragments generated by endonucleolytic cleavage are most likely removed by exonucleolytic decay as well, but these events have not been characterized in detail. Nucleases and other factors (including sequence elements and autoregulatory proteins) required for the promotion or inhibition of these pathways have been identified by both biochemical and genetic methods and systematic attempts to understand their respective roles have begun. sequences whose presence or absence has marked effects on decay rates include the ubiquitous cap and poly(A) tail, sequences that comprise cleavage sites, and sequences that promote poly(A) shortening. The latter are found in the 3'-UTR (untranslated region) and in coding regions. Evidence that poly(A) stimulates initiation, that some destabilization sequences must be translated in order to function, and that premature termination promotes rapid decay indicates a close linkage between the elements regulating decay and components of the protein synthesis apparatus. This linkage, and other data, leads us to propose a model for a functional mRNP. In this model, interactions between factors associated with opposite ends of an stimulate initiation and minimize the rate of entry into the pathways of decay. Events that initiate decay are postulated to be those that can disrupt this functional complex and create substrates for exonucleolytic .

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关键词：

mRNA stability mRNA degradation mRNA decay translation RNA structure poly(A) cap ribosome RNases mRNP