ENAapplication/xmlftp.sra.ebi.ac.uk/vol1/fastq/SRR195/004/SRR1955044/SRR1955044.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR195/003/SRR1955043/SRR1955043.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR195/002/SRR1955042/SRR1955042.fastq.gzprimaryOK2000000GenomicsMarco Blanchette, Stowers Institute for Medical Researchhttps://www.ebi.ac.uk/ena/browser/view/PRJNA280492Homo sapiensThe hnRNP A1 and A2 proteins regulate processes such as alternative pre-mRNA splicing and mRNA stability. Here, we report that a reduction in the levels of hnRNP A1 and A2 by RNA interference or their cytoplasmic retention by osmotic stress drastically increases the transcription of a reporter gene. Based on previous work, we propose that this effect may be linked to a decrease in the activity of the transcription elongation factor P-TEFb. Consistent with this hypothesis, the transcription of the reporter gene was stimulated when the catalytic component of P-TEFb, CDK9, was inhibited with DRB. While low levels of A1/A2 stimulated the association of RNA polymerase II with the reporter gene, they also increased the association of CDK9 with the repressor 7SK RNA, and compromised the recovery of promoter-distal transcription on the Kitlg gene after the release of pausing. Transcriptome analysis revealed that more than 50% of the genes whose expression was affected by the siRNA-mediated depletion of A1/A2 were also affected by DRB. RNA polymerase II-chromatin immunoprecipitation assays on DRB-treated and A1/A2-depleted cells identified a common set of repressed genes displaying increased occupancy of polymerases at promoter-proximal locations, consistent with pausing. Overall, our results suggest that lowering the levels of hnRNP A1/A2 elicits defective transcription elongation on a fraction of P-TEFb-dependent genes, hence favoring the transcription of P-TEFb-independent genes. Overall design: two treatements and one controlENATopoisomerase-inhibitor suppressed, cellular transcription, transcription, ALS19, Helix-destabilizing protein, Heterogeneous nuclear ribonucleoprotein A1, DNA-dependent transcription, N-terminally processed, IBMPFD3, Proteins, DNA-templated, Gene, Hdp, HDP, HNRPA1L3, proteins, function, HNRPA1, Protein Gene Products, Single-strand RNA-binding protein, Gene Proteins, hnRNP A1, hnRNP-A1, D15Ertd119e, bacterial transcription, hnRNP core protein A1, HDP-1, Protein, Gene Products, ALS20, Single-strand-binding protein, Hnrpa1, DNA-dependent., transcription from bacterial-type RNA polymerase promoter, hnrnp-A1human being, human., man0.00.00.00.00.00falseHomo sapiensA function for the hnRNP A1/A2 proteins in transcription elongation2022-05-122015-04-09PRJNA280492GSE676179606