TRANSLATIONAL REGULATION IN MITOCHONDRIAL BIOGENESIS DURING BROWN ADIPOGENESIS

Abstract

The vast majority (>99%) of proteins that constitute functional mitochondria are encoded by nuclear genes. Whether these genes are coordinately regulated at the translation level, and whether they undergo localized translation at the vicinity of mitochondria (as in the situation in yeast) during mitochondrial biogenesis is not well-studied. Using RNA-Seq and ribosome profiling, we investigated translational regulation in different subcellular fractions, during mitochondrial biogenesis, in a genome-wide manner, using brown adipogenesis as a model system. We find that translational changes are first observed around mitochondria before they can be detected at the whole-cell level. Interestingly, mRNAs with a higher frequency of G/C-ending codons are more upregulated translationally. Concurrently, we show that ~1/3 of nuclear-encoded mRNAs for mitochondrial proteins localize to the vicinity of the mitochondria. In conclusion, differential codon recognition and localized translation influence the translation of mRNAs encoding mitochondrial proteins during mitochondrial biogenesis in brown fat differentiation.