2018
DOI: 10.7554/elife.38014
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Decoupling the impact of microRNAs on translational repression versus RNA degradation in embryonic stem cells

Abstract: 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.… Show more

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Cited by 60 publications
(57 citation statements)
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“…P-values are denoted as follows: P < 0.05 (*) and P < 0.01 (**). Moreover, DDX6, the mammalian ortholog of DHH1, was recently demonstrated in humans to be involved in miRNA-driven translational repression, not mRNA destabilization as previously shown in yeast [73]. While paper by Wu et al had assigned optimal and non-optimal designations to codons via the calculation of the CSC derived from ORFeome and SLAM-seq experiments, we noted that some of the findings paralleled ours.…”
Section: Investigating the System Of Codon Bias In Humanssupporting
confidence: 84%
“…P-values are denoted as follows: P < 0.05 (*) and P < 0.01 (**). Moreover, DDX6, the mammalian ortholog of DHH1, was recently demonstrated in humans to be involved in miRNA-driven translational repression, not mRNA destabilization as previously shown in yeast [73]. While paper by Wu et al had assigned optimal and non-optimal designations to codons via the calculation of the CSC derived from ORFeome and SLAM-seq experiments, we noted that some of the findings paralleled ours.…”
Section: Investigating the System Of Codon Bias In Humanssupporting
confidence: 84%
“…DDX6 and P-bodies have also been implicated in microRNA (miRNA)-mediated suppression of RNA translation (Chan and Slack, 2006;Freimer et al, 2018;Kulkarni et al, 2010), suggesting that relief from miRNA-mediated silencing may be another mechanism by which DDX6 suppression affects stem cell potency. In support of this idea, we found that some mRNA targets that changed translation in DDX6 knockdown cells were enriched for binding sites of miRNAs ( Figure S6L) previously implicated in pluripotency control and reprogramming (Leonardo et al, 2012).…”
Section: Ddx6-bound Mrnas Are Translationally Suppressed In P-bodiesmentioning
confidence: 99%
“…Recently, Freimer et al (2018) reported intriguing similarities in translational regulation between Ddx6-deficient mESCs and Dgcr8-deficient mESC, which lack all miRNAs. This observation, together with our finding that some DDX6 targets in hPSCs harbor miRNA recognition sequences, suggests that the effect of DDX6 on cellular potency may be partially explained by its role in miRNA-mediated translational repression.…”
Section: (Legend Continued On Next Page)mentioning
confidence: 99%
“…Different studies have demonstrated that DDX6 helicase regulates gene expression and is involved in the control of the stemness/differentiation process in embryonic [4,5], pluripotent-induced (iPSCs) [37], neural [6] and intestinal [5] stem cells, as well as in neural [5], epidermal [1] and muscular [1,5] progenitors. It has also been demonstrated that the role played by this helicase is related to the protein complexes associated with it [1].…”
Section: Discussionmentioning
confidence: 99%
“…In embryonic stem cells (ESCs), DDX6 silencing increased the expression of transcripts that are targeted by microRNAs. This increase was not related to changes in mRNA stability but was related to the regulation of the translational rate [4]. DDX6 also regulated the translational rate of target mRNAs in human-induced pluripotent stem cells (hIPSCs).…”
Section: Introductionmentioning
confidence: 99%