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Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

ABSTRACT: Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

PROVIDER: PRJNA821543 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18548567.fastq.gz	Fastqsanger.gz
	SRR18548568.fastq.gz	Fastqsanger.gz
	SRR18548569.fastq.gz	Fastqsanger.gz
	SRR18548570.fastq.gz	Fastqsanger.gz
	SRR18548571.fastq.gz	Fastqsanger.gz

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Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

Project description:Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

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Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

Project description:Here, by combining transcriptome and proteome profiling, we identified 228 post-transcriptionally regulated genes with strict regulation at the protein level in PSCs. Among them, 84 genes were found necessary for the survival of several cell types including PSCs, and 20 genes were identified as specific for the survival of PSCs. These 20 proteins were upregulated only in PSCs and not in differentiated cells derived from the three germ layers. Subcellular fractionation of the mRNA showed that the expression level of most of the 20 proteins was regulated at the mRNA localization stage from the nucleus to the cytoplasm in PSCs, but their translation efficiency was unchanged compared with other cell types. Together, these results reveal a critical function of post-transcriptionally regulated genes on PSC survival.

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Post-transcriptionally regulated genes are essential for pluripotent stem cell survival

Project description:The effects of transcription factors on the maintenance and differentiation of pluripotent stem cells (PSCs) have been well studied. However, the importance of post-transcriptional regulatory mechanisms, which cause the quantitative dissociation of mRNA and protein expression, is still little known. Here, by combining transcriptome and proteome profiling, we identified 228 post-transcriptionally regulated genes with strict upregulation at the protein amounts in PSCs. Among them, we found that 84 genes were vital for the survival of PSCs and HDFs, including 20 genes that were specifically necessary for the survival of PSCs. These 20 proteins were upregulated only in PSCs and not in differentiated cells derived from the three germ layers. Subcellular fractionation of the mRNA showed that the expression of most of the 20 proteins was regulated at the mRNA localization stage from the nucleus to the cytoplasm, but their translation efficiency was constant. Together, these results revealed that post-transcriptionally regulated genes have a crucial role in PSC survival.

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ZFP36L2 post-transcriptionally controls acute myeloid leukemia differentiation

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The human cholesterogenic enzymes DHCR14 and LBR are differentially regulated transcriptionally and post-translationally

Project description:Cholesterol synthesis is a tightly regulated process, both transcriptionally and post-translationally. Transcriptional control of cholesterol synthesis is relatively well understood. However, of the ~20 enzymes in cholesterol biosynthesis, post-translational regulation has only been examined for a small number. Three of the four sterol reductases, DHCR7, DHCR14 and LBR, share evolutionary ties with a high level of sequence homology and predicted structural homology. Despite their homology and that they uniquely share the same 14 reductase activity in cholesterol biosynthesis, little is known about the post-translational regulation of DHCR14 and LBR. Using CHO-7 cells stably expressing epitope tagged DHCR14 or LBR we investigated the post-translational regulation of these enzymes. We found that DHCR14 and LBR undergo differential post translational regulation, with DHCR14 being rapidly turned over, triggered by cholesterol and other sterol intermediates while LBR remained stable. DHCR14 is degraded via the ubiquitin-proteasome system and we identified several DHCR14 and DHCR7 putative interaction partners including the E3 ligase WWP2, which plays a role in the basal and cholesterol-mediated regulation of DHCR14. Interestingly, we found that gene expression across an array of human tissues showed that the C14-SRs gene expression is negatively related; one enzyme or the other tends to be predominately expressed in each tissue. Overall, our findings indicate that while LBR tends to be the constitutively active C14-SR, DHCR14 levels are tuneable, responding to the local cellular demands for cholesterol.

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