Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells

eLife

TJ Hu¹  Jacob W Freimer²  Robert Blelloch² 

[1] Department of Urology, University of California, San Francisco, San Francisco, United States;The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, United States;

关键词: DDX6;    microRNA;    post-transcriptional regulation;    translational regulation;    embryonic stem cells;    RNA stability;   

DOI  :  10.7554/eLife.38014

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown