MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 21; pp. 8686 - 8691
• Main Author: Portal, Maximiliano M
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24-05-2011; National Acad Sciences
• Subjects: Basal Metabolism; Biochemistry; Biochemistry, Molecular Biology; Biological Sciences; Cell Line; Cell lines; DNA repair; DNA-directed RNA polymerase; Gene Expression Regulation; Gene regulation; HEK293 cells; Humans; Journalism; Life Sciences; Messenger RNA; MicroRNA; MicroRNAs - physiology; miRNA; Mitochondria; Polypeptides; Post-transcription; Protein Subunits - genetics; Ribonuclease III; Ribonucleic acid; RNA; RNA polymerase; RNA Processing, Post-Transcriptional; RNA, Messenger - metabolism; Three prime untranslated regions; transcription (genetics); Transcription Factor TFIIH - genetics; Transcription factors; Transcription, Genetic; Translation; translation (genetics); Untranslated regions
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1014018108

General transcription factor IIH (TFIIH) is a complex RNA polymerase II basal transcription factor comprising 10 different polypeptides that display activities involved in transcription and DNA repair processes. Although biochemical studies have uncovered TFIIH importance, little is known about how the mRNAs that code for TFIIH subunits are regulated. Here it is shown that mRNAs encoding seven of the TFIIH subunits (p34, p44, p52, p62, XPB, CDK7, and p8) are regulated at the posttranscriptional level in a Dicer-dependent manner. Indeed, abolition of the miRNA pathway induces abnormal accumulation, stabilization, and translational activation of these seven mRNAs. Herein, miR-27a was identified as a key regulator of p44 mRNA. Moreover, miR-27a was shown to destabilize the p44 subunit of the TFIIH complex during the G2-M phase, thereby modulating the transcriptional shutdown observed during this transition. This work is unique in providing a demonstration of global transcriptional regulation through the action of a single miRNA.