Deciphering the Epitranscriptomic Signatures in Cell Fate Determination and Development

Abstract

Precise regulation of transcriptome modulates several vital aspects in an organism that includes gene expression, cellular activities and development, and its perturbation ensuing pathological conditions. Around 150 post-transcriptional modifications of RNA have been identified till date, which are evolutionarily conserved and likewise prevalent across RNA classes including messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), and detected less frequently in small nuclear RNA (snRNA) and microRNAs (miRNA). Among the RNA modifications documented, N6-methyladenosine (m⁶A) is the best characterised till date. Also, N¹-methyladenosine (m¹A), 5-methylcytosine (m⁵C) and pseudouridine (Ψ) are some of the other prominent modifications detected in coding and non-coding RNAs. "Epitranscriptome", ensemble of these post-transcriptional RNA modifications, precisely coordinates gene expression and biological processes. Current literatures suggest the critical involvement of epitranscriptomics in several organisms during early development, contributing to cell fate specification and physiology. Indeed, epitranscriptomics similar to DNA epigenetics involves combinatorial dynamics provided by modified RNA molecules and associated protein complexes, which function as "writers", "erasers" and "readers" of these modifications. A novel code orchestrating gene expression during cell fate determination is generated by the coordinated effects of different classes of modified RNAs and its regulator proteins. In this review, we summarize the current knowhow on N6-methyladenosine (m⁶A), 5-methylcytosine (m⁵C) and pseudouridine (ψ) modifications in RNA, the associated regulator proteins and enumerate how the epitranscriptomic regulations are involved in cell fate determination.

Keywords: Cell fate; Embryonic development; Epitranscriptomics; Post-transcriptional modification; RNA binding protein; Stem cells.