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bioRxiv · 10.1101/594168

Pat1 activates late steps in mRNA decay by multiple mechanisms

Lobel, J. H.·Tibble, R. W.·Gross, J. D.
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Abstract

Pat1 is a hub for mRNA metabolism, acting in pre-mRNA splicing, translation repression and mRNA decay. A critical step in all 5-3 mRNA decay pathways is removal of the 5 cap structure, which precedes and permits digestion of the RNA body by conserved exonucleases. During bulk 5-3 decay, the Pat1/Lsm1-7 complex engages mRNA at the 3 end and promotes hydrolysis of the cap structure by Dcp1/Dcp2 at the 5 end through an unknown mechanism. We reconstitute Pat1 with 5 and 3 decay factors and show how it activates multiple steps in late mRNA decay. First, we find that Pat1 stabilizes binding of the Lsm1-7 complex to RNA using two conserved short-linear interaction motifs. Secondly, Pat1 directly activates decapping by binding elements in the disordered C-terminal extension of Dcp2, alleviating autoinhibition and promoting substrate binding. Our results uncover the molecular mechanism of how separate domains of Pat1 coordinate the assembly and activation of a decapping mRNP that promotes 5-3 mRNA degradation.

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Lobel, J. H., Tibble, R. W., Gross, J. D.. 2019-03-30. Pat1 activates late steps in mRNA decay by multiple mechanisms. https://doi.org/10.1101/594168

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