A transcription-independent role for HIF-1α in modulating microprocessor assembly.

Autor:	Li JN; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Breast Medical Center, National Cheng Kung University Hospital, Tainan, Taiwan.; Research Center for Medical Laboratory Biotechnology, National Cheng Kung University, Tainan, Taiwan., Wang MY; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.; Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan., Ruan JW; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Research Center for Medical Laboratory Biotechnology, National Cheng Kung University, Tainan, Taiwan., Lyu YJ; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan., Weng YH; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Research Center for Medical Laboratory Biotechnology, National Cheng Kung University, Tainan, Taiwan., Brindangnanam P; Department of Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India., Coumar MS; Department of Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Pondicherry 605014, India., Chen PS; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.; Breast Medical Center, National Cheng Kung University Hospital, Tainan, Taiwan.; Research Center for Medical Laboratory Biotechnology, National Cheng Kung University, Tainan, Taiwan.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Oct 28; Vol. 52 (19), pp. 11806-11821.
DOI:	10.1093/nar/gkae792
Abstrakt:	Microprocessor is an essential nuclear complex responsible for the initial RNase-mediated cleavage of primary miRNA, which is a tightly controlled maturation process that requires the proper assembly of Drosha and DGCR8. Unlike previously identified mechanisms directly targeting the enzymatic subunit Drosha, current knowledge about the biological ways of controlling miRNA nuclear maturation through DGCR8 is less addressed. In this study, we unveiled that the microprocessor assembly is governed by a master gene regulator HIF-1α irrespective of its canonical transcriptional activity. First, a widespread protein binding of HIF-1α with DGCR8 instead of Drosha was observed in response to biological stimulations. Similar protein interactions between their corresponding orthologues in model organisms were also observed. After dissecting the essential protein domains, we noticed that HIF-1α suppresses microprocessor assembly via binding to DGCR8. Furthermore, our results showed that HIF-1α hijacks monomeric DGCR8 thus reducing its dimer formation prior to microprocessor assembly, and consequently, the suppressed microprocessor formation and nuclear processing of primary miRNA were demonstrated. In conclusion, here we unveiled the mechanism of how microprocessor assembly is regulated by HIF-1α, which not only demonstrates a non-transcriptional function of nuclear HIF-1α but also provides new molecular insights into the regulation of microprocessor assembly through DGCR8. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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