PIMT/TGS1: An evolving metabolic molecular switch with conserved methyl transferase activity

Rebecca Kristina Edwin; Nagalakshmi Challa; Rahul Sharma; K Satyamoorthy; Kishore Parsa; Parimal Misra

doi:10.1016/j.drudis.2022.04.018

PIMT/TGS1: An evolving metabolic molecular switch with conserved methyl transferase activity

Drug Discov Today. 2022 Aug;27(8):2386-2393. doi: 10.1016/j.drudis.2022.04.018. Epub 2022 Apr 21.

Authors

Rebecca Kristina Edwin¹, Nagalakshmi Challa¹, Rahul Sharma¹, K Satyamoorthy², Kishore Parsa³, Parimal Misra⁴

Affiliations

¹ Centre for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India; Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
² Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
³ Centre for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India. Electronic address: [email protected].
⁴ Centre for Innovation in Molecular and Pharmaceutical Sciences (CIMPS), Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500046, India. Electronic address: [email protected].

PMID: 35462043
DOI: 10.1016/j.drudis.2022.04.018

Abstract

Transcriptional coactivators play a crucial role in regulating gene expression. PRIP interacting protein with methyl transferase domain (PIMT)/trimethyl guanosine synthase 1 (TGS1) is a co-activator interacting protein with an RNA methyl transferase domain. PIMT serves as a bridge between HAT and non-HAT coactivators and differentially modulates gene expression. Disruption of PIMT is embryonic lethal. PIMT regulates hepatic gluconeogenesis and TNF-α-induced insulin resistance in the skeletal muscle. As a methyl transferase, PIMT controls post-transcriptional regulation of HIV-1 and is essential for human telomerase RNA biogenesis. This review comprehensively describes the dual role of PIMT, which promises to be a putative target in metabolic disorders.

Keywords: Co-activator; Glucose metabolism; Metabolism; Methyl transferase; PIMT; PPARγ; PRIP; TGS1; Transcription regulation.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Gene Expression Regulation
Humans
Protein D-Aspartate-L-Isoaspartate Methyltransferase* / genetics
Protein D-Aspartate-L-Isoaspartate Methyltransferase* / metabolism
Protein Domains

Substances

PCMT1 protein, human
Protein D-Aspartate-L-Isoaspartate Methyltransferase