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

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

PROVIDER: PRJNA448913 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6949730.fastq.gz	Fastqsanger.gz
	SRR6949740_1.fastq.gz	Fastqsanger.gz
	SRR6949740_2.fastq.gz	Fastqsanger.gz
	SRR6949750.fastq.gz	Fastqsanger.gz
	SRR6949760.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation

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Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [RIBOseq]

Project description:Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [RIBOseq]

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Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [RNAseq]

Project description:Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [RNAseq]

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Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [miRNA-Seq]

Project description:Synergizing Translational Repression Versus RNA Degradation by miRNAs during T Cell Activation [miRNA-Seq]

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

Project description:This SuperSeries is composed of the SubSeries listed below.

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DDX6 decouples translational repression from RNA degradation of miRNA targets [QuantSeq mRNA]

Project description:Translation and mRNA degradation are intimately connected, yet the mechanisms that regulate them are not fully understood. Here we examine the regulation of translation and mRNA stability in mouse embryonic stem cells (ESCs) and during differentiation. In contrast to previous reports, we found that transcriptional changes account for most of the molecular changes during ESC differentiation. Within ESCs translation level and mRNA stability are positively correlated. The RNA-binding protein DDX6 has been implicated in processes involving both translational repression and mRNA destabilization; in yeast DDX6 connects codon optimality and mRNA stability and in mammals DDX6 is involved in microRNA-mediated repression. We generated DDX6 KO ESCs and found that while there was minimal connection between codon usage and stability changes, the loss of DDX6 leads to the translational depression of microRNA targets. Surprisingly, the translational derepression of microRNA targets occurs without affecting mRNA stability. Furthermore, DDX6 KO ESCs share overlapping phenotypes and global molecular changes with ESCs that completely lack all microRNAs. Together our results demonstrate that the loss of DDX6 decouples the two forms of microRNA induced repression and emphasize that translational repression by microRNAs is underappreciated.

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