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PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling

Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we ident...

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Autores principales: Verma, Mamta, Khan, Mohd. Imran K., Kadumuri, Rajashekar Varma, Chakrapani, Baskar, Awasthi, Sharad, Mahesh, Arun, Govindaraju, Gayathri, Chavali, Pavithra L, Rajavelu, Arumugam, Chavali, Sreenivas, Dhayalan, Arunkumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835222/
https://www.ncbi.nlm.nih.gov/pubmed/33495566
http://dx.doi.org/10.1038/s42003-020-01644-3
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author Verma, Mamta
Khan, Mohd. Imran K.
Kadumuri, Rajashekar Varma
Chakrapani, Baskar
Awasthi, Sharad
Mahesh, Arun
Govindaraju, Gayathri
Chavali, Pavithra L
Rajavelu, Arumugam
Chavali, Sreenivas
Dhayalan, Arunkumar
author_facet Verma, Mamta
Khan, Mohd. Imran K.
Kadumuri, Rajashekar Varma
Chakrapani, Baskar
Awasthi, Sharad
Mahesh, Arun
Govindaraju, Gayathri
Chavali, Pavithra L
Rajavelu, Arumugam
Chavali, Sreenivas
Dhayalan, Arunkumar
author_sort Verma, Mamta
collection PubMed
description Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we identified Retinal dehydrogenase 1 (ALDH1A1) as a potential interaction partner of PRMT3 and confirmed this interaction using different methods. ALDH1A1 regulates variety of cellular processes by catalyzing the conversion of retinaldehyde to retinoic acid. By molecular docking and site-directed mutagenesis, we identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. Our findings show that in addition to regulating protein functions by introducing methylation modifications, PRMT3 could also regulate global gene expression through protein-protein interactions.
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spelling pubmed-78352222021-01-29 PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling Verma, Mamta Khan, Mohd. Imran K. Kadumuri, Rajashekar Varma Chakrapani, Baskar Awasthi, Sharad Mahesh, Arun Govindaraju, Gayathri Chavali, Pavithra L Rajavelu, Arumugam Chavali, Sreenivas Dhayalan, Arunkumar Commun Biol Article Protein arginine methyltransferase 3 (PRMT3) regulates protein functions by introducing asymmetric dimethylation marks at the arginine residues in proteins. However, very little is known about the interaction partners of PRMT3 and their functional outcomes. Using yeast-two hybrid screening, we identified Retinal dehydrogenase 1 (ALDH1A1) as a potential interaction partner of PRMT3 and confirmed this interaction using different methods. ALDH1A1 regulates variety of cellular processes by catalyzing the conversion of retinaldehyde to retinoic acid. By molecular docking and site-directed mutagenesis, we identified the specific residues in the catalytic domain of PRMT3 that facilitate interaction with the C-terminal region of ALDH1A1. PRMT3 inhibits the enzymatic activity of ALDH1A1 and negatively regulates the expression of retinoic acid responsive genes in a methyltransferase activity independent manner. Our findings show that in addition to regulating protein functions by introducing methylation modifications, PRMT3 could also regulate global gene expression through protein-protein interactions. Nature Publishing Group UK 2021-01-25 /pmc/articles/PMC7835222/ /pubmed/33495566 http://dx.doi.org/10.1038/s42003-020-01644-3 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Verma, Mamta
Khan, Mohd. Imran K.
Kadumuri, Rajashekar Varma
Chakrapani, Baskar
Awasthi, Sharad
Mahesh, Arun
Govindaraju, Gayathri
Chavali, Pavithra L
Rajavelu, Arumugam
Chavali, Sreenivas
Dhayalan, Arunkumar
PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
title PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
title_full PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
title_fullStr PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
title_full_unstemmed PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
title_short PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
title_sort prmt3 interacts with aldh1a1 and regulates gene-expression by inhibiting retinoic acid signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835222/
https://www.ncbi.nlm.nih.gov/pubmed/33495566
http://dx.doi.org/10.1038/s42003-020-01644-3
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