Translation-dependent and independent mRNA decay occur through mutually exclusive pathways that are defined by ribosome density during T Cell activation [RNA-Seq]

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 is by targeting mRNAs to translation-dependent degradation (TDD), thus making any increase in protein expression self-limiting. However, 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-induced TDD in mouse primary CD4 T cells. Our data indicate that most cellular transcripts are decayed to some extent in a translation-dependent manner, both in resting and activated cells. Analysis of transcript features revealed that 3’UTR length and ribosome density are major determinants of the magnitude of TDD as well as GC content and amino acid identity. Consistently, upon T cell activation, all transcripts that undergo changes in ribosome density display a corresponding change in their level of TDD. Surprisingly, the amplitude of translation-independent mRNA decay appears as a mirror image of TDD. Moreover, translation-independent decay also responds to changes in ribosome density upon T cell activation but in the opposite direction to those observed for TDD. Our data demonstrate a strong interconnection between mRNA translation and decay in mammalian cells. Furthermore they indicate that ribosome loading is a major determinant of the pathway by which transcripts are degraded within cells