Translation and mRNA degradation are intimately connected, yet the mechanisms that link them are not fully understood. Here we studied these mechanisms in embryonic stem cells (ESCs). Transcripts showed a wide range of stabilities, which correlated with their relative translation levels and that did not change during early ESC differentiation. The protein DHH1 links translation to mRNA stability in yeast; however, loss of the mammalian homolog, DDX6, in ESCs did not disrupt the correlation across transcripts. Instead, the loss of DDX6 led to upregulated translation of microRNA targets, without concurrent changes in mRNA stability. The Ddx6 knockout cells were phenotypically and molecularly similar to cells lacking all microRNAs (Dgcr8 knockout ESCs). These data show that the loss of DDX6 can separate the two canonical functions of microRNAs: translational repression and transcript destabilization. Furthermore, these data uncover a central role for translational repression independent of transcript destabilization in defining the downstream consequences of microRNA loss.
Sequencing data have been deposited in GEO under accession codes GSE112767.
Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE112767).
- Robert Blelloch
- Robert Blelloch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Nahum Sonenberg, McGill University, Canada
© 2018, Freimer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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