PACT establishes a posttranscriptional brake on mitochondrial biogenesis by promoting the maturation of miR-181c

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buir.contributor.authorDoğan, Aslı Ekin
buir.contributor.authorYıldırım, Aslı Dilber
buir.contributor.authorYıldırım, Zehra
buir.contributor.orcidDoğan, Aslı Ekin|0000-0003-1546-7191
buir.contributor.orcidYıldırım, Aslı Dilber|0000-0002-5654-3093
buir.contributor.orcidYıldırım, Zehra|0000-0003-3132-8984
dc.citation.epage15en_US
dc.citation.issueNumber7en_US
dc.citation.spage1en_US
dc.citation.volumeNumber298en_US
dc.contributor.authorDoğan, Aslı Ekin
dc.contributor.authorHamid, Syed M.
dc.contributor.authorYıldırım, Aslı Dilber
dc.contributor.authorYıldırım, Zehra
dc.contributor.authorSen, Ganes
dc.contributor.authorRiera, Celine E.
dc.contributor.authorGottlieb, Roberta A.
dc.contributor.authorErbay, Ebru
dc.date.accessioned2023-02-28T12:45:37Z
dc.date.available2023-02-28T12:45:37Z
dc.date.issued2022-07
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractThe double-stranded RNA-dependent protein kinase activating protein (PACT), an RNA-binding protein that is part of the RNA-induced silencing complex, plays a key role in miR-mediated translational repression. Previous studies showed that PACT regulates the expression of various miRs, selects the miR strand to be loaded onto RNA-induced silencing complex, and determines proper miR length. Apart from PACT's role in mediating the antiviral response in immune cells, what PACT does in other cell types is unknown. Strikingly, it has also been shown that cold exposure leads to marked downregulation of PACT protein in mouse brown adipose tissue (BAT), where mitochondrial biogenesis and metabolism play a central role. Here, we show that PACT establishes a posttranscriptional brake on mitochondrial biogenesis (mitobiogenesis) by promoting the maturation of miR-181c, a key suppressor of mitobiogenesis that has been shown to target mitochondrial complex IV subunit I (Mtco1) and sirtuin 1 (Sirt1). Consistently, we found that a partial reduction in PACT expression is sufficient to enhance mitobiogenesis in brown adipocytes in culture as well as during BAT activation in mice. In conclusion, we demonstrate an unexpected role for PACT in the regulation of mitochondrial biogenesis and energetics in cells and BAT. © 2022 The Authorsen_US
dc.identifier.doi10.1016/j.jbc.2022.102050en_US
dc.identifier.issn00219258
dc.identifier.urihttp://hdl.handle.net/11693/111930
dc.language.isoEnglishen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.en_US
dc.relation.isversionofhttps://dx.doi.org/10.1016/j.jbc.2022.102050en_US
dc.source.titleJournal of Biological Chemistryen_US
dc.subjectBrown adipose tissueen_US
dc.subjectMicro-RNAen_US
dc.subjectMitochondriaen_US
dc.subjectMitochondrial biogenesisen_US
dc.subjectRNAien_US
dc.titlePACT establishes a posttranscriptional brake on mitochondrial biogenesis by promoting the maturation of miR-181cen_US
dc.typeArticleen_US

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