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Emiliano RICCI

Translation has a global impact on mRNA decay during T cell and macrophage activation
When Oct 18, 2019
from 11:00 AM to 12:00 PM
Contact Name Equipe Ricci - Salle des Thèses
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Post-transcriptional control is crucial for regulating protein expression, both basally and in response to extracellular cues. Proper signal transduction requires tight control of both response induction and termination. One way protein expression might be attenuated following cell activation is by targeting mRNAs to translation-dependent degradation (TDD), thus making any increase in protein expression self-limiting. The extent to which TDD is a general mechanism for limiting protein expression is currently unknown. Here we describe a comprehensive analysis of basal and signal-dependent gene expression in primary mouse T cells and macrophages. In order to measure the impact of TDD in regulating gene expression, we performed RNA-Seq, PAS-Seq and ribosome profiling to monitor RNA levels, 3’UTR length, translational efficiency, and RNA degradation transcriptome-wide, both before and after activation of T cells and macrophages. Our data surprisingly indicate that most unstable mRNAs are decayed to some extent in a translation-dependent manner, both in resting and activated cells. Interestingly, the extent of TDD is inversely correlated to the length of the 5’UTR and 3’UTR but not to that of the coding sequence. Furthermore, ribosome density appears to be a main driver of TDD. These unexpected observations highlight the strong interconnection that exists between mRNA translation and untranslated regions in regulating mRNA decay.