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.
- MeSH
- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- adenosin analogy a deriváty metabolismus MeSH
- alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 genetika metabolismus MeSH
- anotace sekvence MeSH
- gen pro FTO genetika metabolismus MeSH
- genetická transkripce MeSH
- genová ontologie MeSH
- HEK293 buňky MeSH
- jaderné proteiny genetika metabolismus MeSH
- lidé MeSH
- mapování interakce mezi proteiny MeSH
- messenger RNA genetika metabolismus MeSH
- methyltransferasy genetika metabolismus MeSH
- N-demethylasy genetika metabolismus MeSH
- nekódující RNA genetika metabolismus MeSH
- oprava DNA MeSH
- protein - isoformy genetika metabolismus MeSH
- replikace DNA MeSH
- vazba proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Eukaryotic mRNAs are modified by several chemical marks which have significant impacts on mRNA biology, gene expression, and cellular metabolism as well as on the survival and development of the whole organism. The most abundant and well-studied mRNA base modifications are m6A and ADAR RNA editing. Recent studies have also identified additional mRNA marks such as m6Am, m5C, m1A and Ψ and studied their roles. Each type of modification is deposited by a specific writer, many types of modification are recognized and interpreted by several different readers and some types of modifications can be removed by eraser enzymes. Several works have addressed the functional relationships between some of the modifications. In this review we provide an overview on the current status of research on the different types of mRNA modifications and about the crosstalk between different marks and its functional consequences.
