Publication details

The comprehensive interactomes of human adenosine RNA methyltransferases and demethylases reveal distinct functional and regulatory features

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Authors

COVELO MOLARES Helena OBRDLÍK Aleš POSTULKOVA I. DOHNÁLKOVÁ Michaela GREGOROVÁ Pavlína GANJI Sri Ranjani POTĚŠIL David GAWRIYSKI L. VARJOSALO M. VAŇÁČOVÁ Štěpánka

Year of publication 2021
Type Article in Periodical
Magazine / Source Nucleic acids research
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://watermark.silverchair.com/gkab900.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtowggLWBgkqhkiG9w0BBwagggLHMIICwwIBADCCArwGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMYI0atmVmxuSJtvGtAgEQgIICjTOr8naIxPbW6AIOXEA-BqaQ4jGkEwiuhTJ9NCzQmkhQdI
Doi http://dx.doi.org/10.1093/nar/gkab900
Keywords PRE-MESSENGER-RNA; SINGLE-STRANDED-DNA; POLYMERASE-II; NUCLEAR-RNA; M(6)A METHYLTRANSFERASE; GENE-EXPRESSION; 7SK SNRNP; P-TEFB; METHYLATION; PROTEIN
Description N6-methyladenosine (m(6)A) and N6,2 '-O-dimethyladenosine (m(6)Am) 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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