Dhh1 promotes translation initiation of ... mRNAs that form structures in their coding sequence

Credit: Lara Crow/ Macmillan Publishers Limited

Remodelling of RNA structures by proteins such as the DEAD-box (DDX) RNA helicases regulates gene expression at various stages. The budding yeast helicase Dhh1 and its human counterpart DDX6 are known to repress translation and activate mRNA decay. Now, Jungfleisch et al. show that Dhh1 promotes translation initiation of a subset of mRNAs that form structures in their coding sequence.

The authors found in budding yeast that Dhh1 promotes translation initiation of the plant Brome mosaic virus (BMV) RNA2 by binding to all parts of the transcript. Because mRNA coding sequences have only rarely been associated with translation regulation, the authors focused on studying this part of the transcript and found a stem-loop structure that strongly inhibited its translation in cells lacking Dhh1.

Next, through RNA–protein crosslinking and translation analyses, the authors identified 245 yeast transcripts that are bound by Dhh1, and the translation of which is reduced in cells lacking Dhh1. Binding of Dhh1 around the translation initiation codon was much higher for these mRNAs than in other cellular mRNAs, and ribosome profiling analyses further supported a role for Dhh1 in promoting translation initiation at these transcripts.

Compared with other mRNAs, those that depend on Dhh1 for their translation have longer and more structured coding sequences. Similarly, their human homologues also have relatively long, structured coding sequences, and translation of one such mRNA, encoding the oncogene PTCH1, was found to depend on DDX6.

This study reveals a new mechanism of translation regulation that is conserved from yeast to humans. Relying on DDX helicases and on RNA structures, including those present in coding sequences, this mechanism controls translation initiation of specific genes and can be exploited by RNA viruses.