Role of RNA methyltransferases in tissue renewal and pathology

Abstract

Over the last five decades more than 100 types of RNA modifications have been identified in organism of all kingdoms of life, yet their function and biological relevance remain largely elusive. The recent development of transcriptome-wide techniques to detect RNA modifications such as N(6)-methyladenosine (m(6)A) and 5-methylcytidine (m(5)C) has not only created a new field of research 'the epitranscriptome' but also featured essential regulatory roles of RNA methylation in a wide range of fundamental cellular processes. Here, we discuss the current knowledge of m(6)A and m(5)C RNA methylation pathways and summarize how they impact normal tissues and contribute to human disease.

Figure 1

Regulation and function of RNA methylation. C⁵-methylcytidine (m⁵C) is a common modification in (a) tRNAs and (b) other non-coding RNAs (ncRNAs). NSun2, NSun4 and Dnmt2 can catalyze methylation of cytosine-5 but no m⁵C-demethylases have been reported yet (a and b). (c) N6-methyladenosine (m⁶A) is an abundant internal modification in mRNA. Its deposition is dynamically regulated by methylases (Mettl3 and Mettl14) and demethylases (Fto and AlkBH5). Accurate and adequate methylation levels dictate the fate, processing, interaction with ‘readers’ (YTHDF, HUR) and further function of methylated RNAs. All reported molecular functions relate to the regulation of transcriptional and translational processes.