Why do we study mRNA translation?

Gene expression is ultimately the sum of events, including transcription, translation, and mRNA and protein degradation, that regulate cellular protein content. Translational control is a particularly important step in gene expression for short-term adaptation to changing metabolic conditions and is a fundamental mechanism used in the early adaptive response of cells to diabetes.  In response to hyperglycemia, the proteins that determine which cellular mRNAs are made into proteins exhibit an increased form of post-translational glycosylation known as O-GlcNAcylation.  In order to determine the extent to which O-GlcNAcylation affects retinal gene expression, we used next-generation sequencing to evaluate total mRNA abundances, and ribosome profiling was used to determine which mRNAs were actively being translated into protein. Remarkably, ~19% of the retinal transcriptome exhibits variation in ribosome density in response to enhanced O-GlcNAcylation.

O-GlcNAcylation alters mRNA translation in the retina. Mice were administered the O-GlcNAcase inhibitor TMG or PBS vehicle as a control.  Retinal gene expression was analyzed to assess changes in total mRNA abundance by RNA-Seq and nuclease-resistant ribosome protected fragments (RPF) by Ribo-Seq.  Changes in mRNA abundance (x-axis) and mRNA translation (y-axis) following TMG administration were compared. Significant differences are indicated in purple (translation), green (transcription), or blue (both translation and transcription).