Messenger RNA decay occurs via two major pathways (3' to 5' and 5' to 3' pathways) that are conserved in all eukaryotes. A key feature of these pathways is that mRNAs are targeted for degradation only after they have undergone deadenylation so that polyadenylated mRNAs are not attacked. Thus, in the 5' to 3' pathway, oligoadenylated mRNAs (but not polyadenylated mRNAs) are selectively decapped and then degraded in a 5' to 3' exonucleolytic manner. Here, normal rates of decapping require the decapping activator, the Lsm1-7-Pat1 complex. This complex has a strong intrinsic binding preference for oligoadenylated mRNAs over polyadenylated mRNAs and such preferential binding ability is crucial for its mRNA decay function. This suggests that this complex contributes to the deadenylation dependence of decapping in the 5' to 3' pathway by selectively targeting oligoadenylated messages for decapping. The Lsm1-7-Pat1 complex is also capable of recognizing the presence of U-tracts at the 3'-end of RNA and such recognition appears to be important in facilitating the decapping and 5' to 3' decay of histone mRNAs in response to oligouridylation. Thus, this complex influences decapping event at the 5'-end by recognizing simple sequence features at the 3'-end of the mRNA. Additional studies implicate this complex in the inhibition of exosome mediated 3' to 5' decay of mRNAs raising the possibility that in vivo, the major mode of decay of an mRNA could be determined by the efficiency of binding of the Lsm1-7-Pat1 complex to that mRNA.

• PMID: 19279404
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Journal Article | Research Support, N.I.H., Extramural | Research Support, U.S. Gov't, Non-P.H.S.

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Tharun S

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