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Translation-dependent and -independent mRNA decay occur through mutually exclusive pathways defined by ribosome density during T cell activation.
Genome Res, 34(3):394-409.
mRNA translation and decay are tightly interconnected processes both in thecontext of mRNA quality-control pathways and for the degradation of functionalmRNAs. Cotranslational mRNA degradation through codon usage, ribosome collisions,and the recruitment of specific proteins to ribosomes is an important determinantof mRNA turnover. However, the extent to which translation-dependent mRNA decay(TDD) and translation-independent mRNA decay (TID) pathways participate in thedegradation of mRNAs has not been studied yet. Here we describe a comprehensiveanalysis of basal and signal-induced TDD and TID in mouse primary CD4(+) T cells.Our results indicate that most cellular transcripts are decayed to some extent ina translation-dependent manner. Our analysis further identifies the length ofuntranslated regions, the density of ribosomes, and GC3 content as importantdeterminants of TDD magnitude. Consistently, all transcripts that undergo changesin ribosome density within their coding sequence upon T cell activation display acorresponding change in their TDD level. Moreover, we reveal a dynamic modulationin the relationship between GC3 content and TDD upon T cell activation, with areversal in the impact of GC3- and AU3-rich codons. Altogether, our data show astrong and dynamic interconnection between mRNA translation and decay inmammalian primary cells.
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