Epitranscriptomic Code and Its Alterations in Human Disease

Abstract

Innovations in epitranscriptomics have resulted in the identification of more than 160 RNA modifications to date. These developments, together with the recent discovery of writers, readers, and erasers of modifications occurring across a wide range of RNAs and tissue types, have led to a surge in integrative approaches for transcriptome-wide mapping of modifications and protein-RNA interaction profiles of epitranscriptome players. RNA modification maps and crosstalk between them have begun to elucidate the role of modifications as signaling switches, entertaining the notion of an epitranscriptomic code as a driver of the post-transcriptional fate of RNA. Emerging single-molecule sequencing technologies and development of antibodies specific to various RNA modifications could enable charting of transcript-specific epitranscriptomic marks across cell types and their alterations in disease.

Keywords: RNA metabolism; RNA modifications; next-generation sequencing; post-transcriptional regulation; regulatory networks.

Figure 1:. Frequently occurring chemical modifications in mRNA and their currently known writers, readers, and erasers.

Readers and eraser proteins are only listed for m⁶A modification type. A comprehensive list of RNA modifications along with their currently known enzymes are listed in Table 1.

Figure 2:. Emerging concept of the epitranscriptome code governing the fate of different transcript isoforms of a gene across tissue types.

Although a combination of transcript isoforms of a gene are expressed in a tissue their dynamic tissue/cell-type specific regulation by different modification enzymes (Writers, Readers and Erasers) via epitranscriptome code, determines the differential post-transcriptional regulatory fate of an RNA molecule resulting from a loci. Such combinatorial epitranscriptome marks specific to an RNA transcript originating from a genic locus, can dictate its splicing, stability, localization as well as translation status, providing a precise cell-type specific spatiotemporal context for regulation.