دورية أكاديمية
The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.
العنوان: | The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function. |
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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 |
تدمد: | 2041-1723 |
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DOI: | 10.1038/s41467-023-41304-8 |