“RNA modifications have already been linked to human diseases including cancer, cardiovascular disease, neurological disorders birth defects”
Epitranscriptomics
Epigenetic modifications regulate gene expression to determine cell fate and responses to environmental stimuli. The field of epitranscriptomics examines the recently deciphered form of gene expression regulation that is mediated by type and site-specific RNA modifications.
RNA m6A modification
- m6A is an abundant and conserved RNA modification in eukaryotic RNAs that affects RNA fate and is characterized by preferential deposition within the RRACH motif and enrichment in mRNA coding sequences and 3′-untranslated regions.
- The RNA methyltransferase complex, comprising of the methyltransferase-like 3 (METTL3)/METTL14 (methyltransferase-like 14) core subunit and other cofactors, is responsible for the deposition of m6A on mRNA, where METTL3 is the catalytic subunit and METTL14 is crucial for target recognition.
- RNA plays a central role in central dogma of molecular biology and is responsible for transmitting the genetic information encoded by DNA into functional proteins. There are different types of RNA molecules that are involved in the regulation of several biological processes, including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), microRNA (miRNA), long noncoding RNA (lncRNA), etc. Analogous to DNA or histone modifications , RNA molecules contain numerous chemical modifications . N7-methylguanosine (m7G), N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), pseudouridine (Ψ), and 2′-O-methylation (Nm), cap N6,2′-O-dimethyladenosine (m6Am), N4-acetylcytidine (Ac4C) have been identified in mammalian mRNA
RNA m5C modifications
The formation of m5C indicates the installation of a methyl group on the fifth carbon of cytosine in CpG islands, which is regulated by m5C methyltransferases and demethylases. The so-called m5C “writer” typically possesses highly conserved functional regions that are present in other members of the enzyme family. Numerous m5C writers participate in the methylation of extensive RNAs and epigenetic regulation.
The functions of m5C writers and readers are believed to regulate gene expression at the post-transcription level and are involved in cellular metabolism and movement