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
• Adaptor Proteins, Signal Transducing genetics   metabolism   MeSH
• Adenosine analogs & derivatives   metabolism   MeSH
• AlkB Homolog 5, RNA Demethylase genetics   metabolism   MeSH
• Molecular Sequence Annotation MeSH
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics   metabolism   MeSH
• Transcription, Genetic MeSH
• Gene Ontology MeSH
• HEK293 Cells MeSH
• Nuclear Proteins genetics   metabolism   MeSH
• Humans MeSH
• Protein Interaction Mapping MeSH
• RNA, Messenger genetics   metabolism   MeSH
• Methyltransferases genetics   metabolism   MeSH
• Oxidoreductases, N-Demethylating genetics   metabolism   MeSH
• RNA, Untranslated genetics   metabolism   MeSH
• DNA Repair MeSH
• Protein Isoforms genetics   metabolism   MeSH
• DNA Replication MeSH
• Protein Binding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adaptor Proteins, Signal Transducing MeSH
• Adenosine MeSH
• AlkB Homolog 5, RNA Demethylase MeSH
• ALKBH5 protein, human MeSH Browser
• FTO protein, human MeSH Browser
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO MeSH
• Nuclear Proteins MeSH
• RNA, Messenger MeSH
• Methyltransferases MeSH
• METTL16 protein, human MeSH Browser
• Oxidoreductases, N-Demethylating MeSH
• N-methyladenosine MeSH Browser
• N(6),N(6)-dimethyladenosine MeSH Browser
• RNA, Untranslated MeSH
• PCIF1 protein, human MeSH Browser
• Protein Isoforms 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.

• Keywords
• ADAR, Inosine, epitranscriptome, m1A, m5C, m6A, m6Am, pseudouridine,
• MeSH
• Epigenesis, Genetic * MeSH
• Epigenomics methods   MeSH
• Humans MeSH
• RNA, Messenger genetics   metabolism   MeSH
• RNA Processing, Post-Transcriptional * MeSH
• Transcriptome * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• RNA, Messenger MeSH