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Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing

The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a s...

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Autores principales: Banerjee, Ayan, Vest, Katherine E., Pavlath, Grace K., Corbett, Anita H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737383/
https://www.ncbi.nlm.nih.gov/pubmed/28977530
http://dx.doi.org/10.1093/nar/gkx786
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author Banerjee, Ayan
Vest, Katherine E.
Pavlath, Grace K.
Corbett, Anita H.
author_facet Banerjee, Ayan
Vest, Katherine E.
Pavlath, Grace K.
Corbett, Anita H.
author_sort Banerjee, Ayan
collection PubMed
description The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a specific form of muscular dystrophy termed oculopharyngeal muscular dystrophy (OPMD). Despite the tissue-specific pathology that occurs in this disease, only recently have studies of PABPN1 begun to explore the role of this protein in skeletal muscle. We have used co-immunoprecipitation and mass spectrometry to identify proteins that interact with PABPN1 in mouse skeletal muscles. Among the interacting proteins we identified Matrin 3 (MATR3) as a novel protein interactor of PABPN1. The MATR3 gene is mutated in a form of distal myopathy and amyotrophic lateral sclerosis (ALS). We demonstrate, that like PABPN1, MATR3 is critical for myogenesis. Furthermore, MATR3 controls critical aspects of RNA processing including alternative polyadenylation and intron retention. We provide evidence that MATR3 also binds and regulates the levels of long non-coding RNA (lncRNA) Neat1 and together with PABPN1 is required for normal paraspeckle function. We demonstrate that PABPN1 and MATR3 are required for paraspeckles, as well as for adenosine to inosine (A to I) RNA editing of Ctn RNA in muscle cells. We provide a functional link between PABPN1 and MATR3 through regulation of a common lncRNA target with downstream impact on paraspeckle morphology and function. We extend our analysis to a mouse model of OPMD and demonstrate altered paraspeckle morphology in the presence of endogenous levels of alanine-expanded PABPN1. In this study, we report protein-binding partners of PABPN1, which could provide insight into novel functions of PABPN1 in skeletal muscle and identify proteins that could be sequestered with alanine-expanded PABPN1 in the nuclear aggregates found in OPMD.
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spelling pubmed-57373832018-01-08 Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing Banerjee, Ayan Vest, Katherine E. Pavlath, Grace K. Corbett, Anita H. Nucleic Acids Res Molecular Biology The polyadenylate binding protein 1 (PABPN1) is a ubiquitously expressed RNA binding protein vital for multiple steps in RNA metabolism. Although PABPN1 plays a critical role in the regulation of RNA processing, mutation of the gene encoding this ubiquitously expressed RNA binding protein causes a specific form of muscular dystrophy termed oculopharyngeal muscular dystrophy (OPMD). Despite the tissue-specific pathology that occurs in this disease, only recently have studies of PABPN1 begun to explore the role of this protein in skeletal muscle. We have used co-immunoprecipitation and mass spectrometry to identify proteins that interact with PABPN1 in mouse skeletal muscles. Among the interacting proteins we identified Matrin 3 (MATR3) as a novel protein interactor of PABPN1. The MATR3 gene is mutated in a form of distal myopathy and amyotrophic lateral sclerosis (ALS). We demonstrate, that like PABPN1, MATR3 is critical for myogenesis. Furthermore, MATR3 controls critical aspects of RNA processing including alternative polyadenylation and intron retention. We provide evidence that MATR3 also binds and regulates the levels of long non-coding RNA (lncRNA) Neat1 and together with PABPN1 is required for normal paraspeckle function. We demonstrate that PABPN1 and MATR3 are required for paraspeckles, as well as for adenosine to inosine (A to I) RNA editing of Ctn RNA in muscle cells. We provide a functional link between PABPN1 and MATR3 through regulation of a common lncRNA target with downstream impact on paraspeckle morphology and function. We extend our analysis to a mouse model of OPMD and demonstrate altered paraspeckle morphology in the presence of endogenous levels of alanine-expanded PABPN1. In this study, we report protein-binding partners of PABPN1, which could provide insight into novel functions of PABPN1 in skeletal muscle and identify proteins that could be sequestered with alanine-expanded PABPN1 in the nuclear aggregates found in OPMD. Oxford University Press 2017-10-13 2017-09-07 /pmc/articles/PMC5737383/ /pubmed/28977530 http://dx.doi.org/10.1093/nar/gkx786 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Banerjee, Ayan
Vest, Katherine E.
Pavlath, Grace K.
Corbett, Anita H.
Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing
title Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing
title_full Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing
title_fullStr Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing
title_full_unstemmed Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing
title_short Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing
title_sort nuclear poly(a) binding protein 1 (pabpn1) and matrin3 interact in muscle cells and regulate rna processing
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5737383/
https://www.ncbi.nlm.nih.gov/pubmed/28977530
http://dx.doi.org/10.1093/nar/gkx786
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