Aug 12 2015 General and miRNA-mediated mRNA degradation occurs on ribosome complexes in Drosophila cells

mRNA degradation in Drosophila cells

mRNA degradation and translation are two processes crucial for posttranscriptional gene regulation. While the strong interconnection of mRNA degradation and translation has been noted for many years, it has led to the hypothesis that mRNAs could be degraded on the ribosome.

We have recently published a study that strongly supports the hypothesis that the ribosome is a very general site not only for general 5' to 3' mRNA degradation in Drosophila but also for the miRNA-mediated mRNA degradation pathway:

Abstract

The translation and degradation of mRNAs are two key steps in gene expression that are highly regulated and targeted by many factors, including microRNAs (miRNAs). While it is well established that translation and mRNA degradation are tightly coupled, it is still not entirely clear where in the cell mRNA degradation takes place. In this study, we investigated the possibility of mRNA degradation on the ribosome in Drosophila cells. Using polysome profiles and ribosome affinity purification, we could demonstrate the copurification of various deadenylation and decapping factors with ribosome complexes. Also, AGO1 and GW182, two key factors in the miRNA-mediated mRNA degradation pathway, were associated with ribosome complexes. Their copurification was dependent on intact mRNAs, suggesting the association of these factors with the mRNA rather than the ribosome itself. Furthermore, we isolated decapped mRNA degradation intermediates from ribosome complexes and performed high-throughput sequencing analysis. Interestingly, 93% of the decapped mRNA fragments (approximately 12,000) could be detected at the same relative abundance on ribosome complexes and in cell lysates. In summary, our findings strongly indicate the association of the majority of bulk mRNAs as well as mRNAs targeted by miRNAs with the ribosome during their degradation.