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

Mamta Verma; Mohd Imran K. Khan; Rajashekar Varma Kadumuri; Baskar Chakrapani; Sharad Awasthi; Arun Mahesh; Gayathri Govindaraju; Pavithra L. Chavali; Arumugam Rajavelu; Sreenivas Chavali; Arunkumar Dhayalan

doi:10.1038/s42003-020-01644-3

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

Mamta Verma
, Mohd Imran K. Khan
, Rajashekar Varma Kadumuri
, Baskar Chakrapani
, Sharad Awasthi
, Arun Mahesh
, Gayathri Govindaraju
, Pavithra L. Chavali
, Arumugam Rajavelu
, Sreenivas Chavali
, Arunkumar Dhayalan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

204 Downloads (Pure)

Abstract

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.

Original language	English
Article number	109
Journal	Communications Biology
Volume	4
DOIs	https://doi.org/10.1038/s42003-020-01644-3
Publication status	Published - 25 Jan 2021
Externally published	Yes

Bibliographical note

Funding Information:
This work was funded by the Innovative Young Biotechnologist Award (Grant No. BT/ 03/IYBA/2010; A.D. and M.V.), Ramalingaswami Re-entry Fellowship (BT/RLF/Re- entry/33/2018; P.L.C., BT/RLF/Re-entry/05/2018; S.C.), Department of Biotechnology; Science & Engineering Research Board (Grant No. SR/FT/LS-28/2012; A.D.; SRG/2019/ 001785; S.C.); IISER Tirupati postdoctoral fellowship (R.V.K.); University Grants Commission (UGC-BSR Junior and Senior Research Fellowships to M.I.K.K. and A.M.); Council of Scientific and Industrial Research, Government of India (Junior and Senior Research Fellowships to B.C. and S.A.); RGCB Intramural grant (A.R.) and IISER Tir-upati seed grant (S.C.). We thank DST-FIST and UGC-Special Assistant Programme (SAP) funded instrumentation facilities and the BUILDER Instrumentation Facility, Pondicherry University. We thank Dr. Shalmoli Bhattacharyya, PGIMER, Chandigarh for kindly sharing the ALDEFLUOR Reagent for preliminary experiments.

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry,Genetics and Molecular Biology
General Agricultural and Biological Sciences

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PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling
Copyright 2022 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.87 MBLicence: CC BY

Cite this

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title = "PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling",

abstract = "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.",

author = "Mamta Verma and Khan, \{Mohd Imran K.\} and Kadumuri, \{Rajashekar Varma\} and Baskar Chakrapani and Sharad Awasthi and Arun Mahesh and Gayathri Govindaraju and Chavali, \{Pavithra L.\} and Arumugam Rajavelu and Sreenivas Chavali and Arunkumar Dhayalan",

note = "Funding Information: This work was funded by the Innovative Young Biotechnologist Award (Grant No. BT/ 03/IYBA/2010; A.D. and M.V.), Ramalingaswami Re-entry Fellowship (BT/RLF/Re- entry/33/2018; P.L.C., BT/RLF/Re-entry/05/2018; S.C.), Department of Biotechnology; Science \& Engineering Research Board (Grant No. SR/FT/LS-28/2012; A.D.; SRG/2019/ 001785; S.C.); IISER Tirupati postdoctoral fellowship (R.V.K.); University Grants Commission (UGC-BSR Junior and Senior Research Fellowships to M.I.K.K. and A.M.); Council of Scientific and Industrial Research, Government of India (Junior and Senior Research Fellowships to B.C. and S.A.); RGCB Intramural grant (A.R.) and IISER Tir-upati seed grant (S.C.). We thank DST-FIST and UGC-Special Assistant Programme (SAP) funded instrumentation facilities and the BUILDER Instrumentation Facility, Pondicherry University. We thank Dr. Shalmoli Bhattacharyya, PGIMER, Chandigarh for kindly sharing the ALDEFLUOR Reagent for preliminary experiments. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

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doi = "10.1038/s42003-020-01644-3",

language = "English",

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journal = "Communications Biology",

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AU - Verma, Mamta

AU - Khan, Mohd Imran K.

AU - Kadumuri, Rajashekar Varma

AU - Chakrapani, Baskar

AU - Awasthi, Sharad

AU - Mahesh, Arun

AU - Govindaraju, Gayathri

AU - Chavali, Pavithra L.

AU - Rajavelu, Arumugam

AU - Chavali, Sreenivas

AU - Dhayalan, Arunkumar

N1 - Funding Information: This work was funded by the Innovative Young Biotechnologist Award (Grant No. BT/ 03/IYBA/2010; A.D. and M.V.), Ramalingaswami Re-entry Fellowship (BT/RLF/Re- entry/33/2018; P.L.C., BT/RLF/Re-entry/05/2018; S.C.), Department of Biotechnology; Science & Engineering Research Board (Grant No. SR/FT/LS-28/2012; A.D.; SRG/2019/ 001785; S.C.); IISER Tirupati postdoctoral fellowship (R.V.K.); University Grants Commission (UGC-BSR Junior and Senior Research Fellowships to M.I.K.K. and A.M.); Council of Scientific and Industrial Research, Government of India (Junior and Senior Research Fellowships to B.C. and S.A.); RGCB Intramural grant (A.R.) and IISER Tir-upati seed grant (S.C.). We thank DST-FIST and UGC-Special Assistant Programme (SAP) funded instrumentation facilities and the BUILDER Instrumentation Facility, Pondicherry University. We thank Dr. Shalmoli Bhattacharyya, PGIMER, Chandigarh for kindly sharing the ALDEFLUOR Reagent for preliminary experiments. Publisher Copyright: © 2021, The Author(s).

PY - 2021/1/25

Y1 - 2021/1/25

N2 - 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.

AB - 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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DO - 10.1038/s42003-020-01644-3

M3 - Article

C2 - 33495566

AN - SCOPUS:85099762457

SN - 2399-3642

VL - 4

JO - Communications Biology

JF - Communications Biology

M1 - 109

ER -

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

Abstract

Bibliographical note

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