The Comprehensive Interactomes of Human Adenosine RNA Methyltransferases and Demethylases Reveal Distinct Functional and Regulatory Features

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2021 Oct 11

PMID 34634806

Citations 25

Authors

Helena Covelo-Molares

Ales Obrdlik

Ivana Postulkova

Michaela Dohnalkova

Pavlina Gregorova

Ranjani Ganji

David Potesil

Lisa Gawriyski

Markku Varjosalo

Stepanka Vanacova

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.

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