Pluto Bioinformatics

GSE144841: 4EHP and GIGYF1/2 induce translation-coupled messenger RNA decay

Bulk RNA sequencing

Although canonical mRNA degradation is generally recognized to be translation dependent, our understanding of the molecular events that coordinate ribosome movement with the decay machinery is still limited. Here, we show that the 4EHPGIGYF1/2 complex triggers co-translational mRNA decay as a result of altered ribosome activity during elongation. Human cells lacking 4EHP and GIGYF1 and 2 proteins accumulate transcripts known to be degraded in a translation dependent manner or with prominent ribosome pausing. These include mRNAs encoding secretory and membrane-bound proteins or specific tubulin isotypes, among others. 4EHPGIGYF1/2 fails to reduce target mRNA levels in the absence of ribosome stalling or upon disruption of its interaction with the cap structure, DDX6 and a GYF domain-associated protein. Our studies reveal how a repressor complex linked to neurological disorders minimizes the protein output of a subset of mRNAs. SOURCE: Ramona Weber (ramona.weber@tuebingen.mpg.de) - Max Planck Institute for Developmental Biology