2. Academic Validation
  3. PRMT3 interacts with ALDH1A1 and regulates gene-expression by inhibiting retinoic acid signaling

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

  • Commun Biol. 2021 Jan 25;4(1):109. doi: 10.1038/s42003-020-01644-3.
Mamta Verma # 1,  Mohd Imran K Khan # 1,  Rajashekar Varma Kadumuri 2,  Baskar Chakrapani 1,  Sharad Awasthi 1,  Arun Mahesh 1,  Gayathri Govindaraju 3,  Pavithra L Chavali 4,  Arumugam Rajavelu 3,  Sreenivas Chavali 5,  Arunkumar Dhayalan 6
Affiliations

Affiliations

  • 1 Department of Biotechnology, Pondicherry University, Puducherry, 605014, India.
  • 2 Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, Andhra Pradesh, 517507, India.
  • 3 Interdisciplinary Biology, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, 695014, India.
  • 4 CSIR-Centre for Cellular & Molecular Biology, Hyderabad, Telangana, 500007, India.
  • 5 Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Tirupati, Andhra Pradesh, 517507, India. schavali@iisertirupati.ac.in.
  • 6 Department of Biotechnology, Pondicherry University, Puducherry, 605014, India. arun.dbt@pondiuni.edu.in.
  • # Contributed equally.
PMID: 33495566 DOI: 10.1038/s42003-020-01644-3
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.

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