Sunday, January 5, 2014

Ribosome profiling confirms widespread stop codon readthrough in flies

A recent eLife paper from the Weissman lab at UCSF uses high-throughput ribosome profiling to show that many Drosophila melanogaster (fruitfly) genes undergo an unusual translation process called stop codon readthrough - confirming many of, and expanding on, our earlier predictions based on computational comparative genomics. Stop codon readthrough occurs when a translating ribosome reaches an in-frame stop codon in an mRNA but, instead of terminating as usual, continues on with translation - as if the stop codon were a sense codon. This gives rise to a protein isoform with an extended C-terminal region, potentially modifying its function or localization.

Stop codon readthrough is a long-known but fairly obscure "recoding" mechanism, which wasn't believed to play a widespread role in metazoan gene expression, save for selenoproteins and a few other intriguing but isolated examples. Now we know that it actually affects hundreds of fly genes - and moreover that, in many cases, the products confer biological functions conserved throughout many millions of years of evolution.