Matches in SemOpenAlex for { <https://semopenalex.org/work/W2970449545> ?p ?o ?g. }
- W2970449545 abstract "Abstract In eukaryotes, the elongation phase of transcription by RNA polymerase II (RNAP II) is regulated by the transcription elongation factor b (P-TEFb), composed of Cyclin-T1 and cyclin-dependent kinase 9. The release of RNAP II is mediated by phosphorylation through P-TEFb that in turn is under control by the inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex. The 7SK snRNP consists of the 7SK non-coding RNA and the proteins MEPCE, LARP7, and HEXIM1/2. Biallelic LARP7 loss-of-function variants underlie Alazami syndrome characterized by growth retardation and intellectual disability. We report a boy with global developmental delay and seizures carrying the de novo MEPCE nonsense variant c.1552 C > T/p.(Arg518*). mRNA and protein analyses identified nonsense-mediated mRNA decay to underlie the decreased amount of MEPCE in patient fibroblasts followed by LARP7 and 7SK snRNA downregulation and HEXIM1 upregulation. Reduced binding of HEXIM1 to Cyclin-T1, hyperphosphorylation of the RNAP II C-terminal domain, and upregulated expression of ID2 , ID3 , MRPL11 and snRNAs U1, U2 and U4 in patient cells are suggestive of enhanced activation of P-TEFb. Flavopiridol treatment and ectopic MEPCE protein expression in patient fibroblasts rescued increased expression of six RNAP II-sensitive genes and suggested a possible repressive effect of MEPCE on P-TEFb-dependent transcription of specific genes." @default.
- W2970449545 created "2019-09-05" @default.
- W2970449545 creator A5013116560 @default.
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- W2970449545 date "2019-08-29" @default.
- W2970449545 modified "2023-09-27" @default.
- W2970449545 title "de novo MEPCE nonsense variant associated with a neurodevelopmental disorder causes disintegration of 7SK snRNP and enhanced RNA polymerase II activation" @default.
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- W2970449545 doi "https://doi.org/10.1038/s41598-019-49032-0" @default.
- W2970449545 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6715695" @default.
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- W2970449545 hasPublicationYear "2019" @default.
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