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The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.

التفاصيل البيبلوغرافية
العنوان: The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.
المؤلفون: Mihaylov SR; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.; Kinases and Brain Development Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Castelli LM; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK., Lin YH; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK., Gül A; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK., Soni N; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK., Hastings C; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK., Flynn HR; Proteomics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Păun O; Neural Stem Cell Biology Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Dickman MJ; Department of Chemical and Biological Engineering, Sir Robert Hadfield Building, University of Sheffield, Mappin Street, Sheffield, S1 3JD, UK.; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK., Snijders AP; Proteomics Science Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.; Life Science Mass Spectrometry, Bruker Daltonics, Banner Lane, Coventry, CV4 9GH, UK., Goldstone R; Bioinformatics and Biostatistics Science and Technology Platform, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Bandmann O; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.; Healthy Lifespan Institute (HELSI), University of Sheffield, Western Bank, Sheffield, S10 2TN, UK., Shelkovnikova TA; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK., Mortiboys H; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK.; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.; Healthy Lifespan Institute (HELSI), University of Sheffield, Western Bank, Sheffield, S10 2TN, UK., Ultanir SK; Kinases and Brain Development Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK., Hautbergue GM; Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, 385 Glossop Road, Sheffield, S10 2HQ, UK. g.hautbergue@sheffield.ac.uk.; Neuroscience Institute, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. g.hautbergue@sheffield.ac.uk.; Healthy Lifespan Institute (HELSI), University of Sheffield, Western Bank, Sheffield, S10 2TN, UK. g.hautbergue@sheffield.ac.uk.
المصدر: Nature communications [Nat Commun] 2023 Sep 07; Vol. 14 (1), pp. 5496. Date of Electronic Publication: 2023 Sep 07.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: RNA* , RNA Transport*, Humans ; Active Transport, Cell Nucleus ; Gene Expression ; Homeostasis
مستخلص: PGC-1α plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and an RNA recognition motif, however the RNA-processing function(s) were poorly investigated over the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1. Inducible depletion of PGC-1α and expression of RNAi-resistant RS-deleted PGC-1α further demonstrate that its RNA/NXF1-binding activity is required for the nuclear export of some canonical mitochondrial-related mRNAs and mitochondrial homeostasis. Genome-wide investigations reveal that the nuclear export function is not strictly linked to promoter-binding, identifying in turn novel regulatory targets of PGC-1α in non-homologous end-joining and nucleocytoplasmic transport. These findings provide new directions to further elucidate the roles of PGC-1α in gene expression, metabolic disorders, aging and neurodegeneration.
(© 2023. Springer Nature Limited.)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; F-1301 United Kingdom PUK_ Parkinson's UK; FC001201 United Kingdom ARC_ Arthritis Research UK; MR/R024162/1 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 63231-63-0 (RNA)
0 (PPARGC1A protein, human)
تواريخ الأحداث: Date Created: 20230907 Date Completed: 20230913 Latest Revision: 20240214
رمز التحديث: 20240214
مُعرف محوري في PubMed: PMC10485026
DOI: 10.1038/s41467-023-41304-8
PMID: 37679383
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-023-41304-8