Novel insight into the regulatory roles of diverse RNA modifications: Re-defining the bridge between transcription and translation

Abstract

RNA modifications can be added or removed by a variety of enzymes that catalyse the necessary reactions, and these modifications play roles in essential molecular mechanisms. The prevalent modifications on mRNA include N6-methyladenosine (m 6 A), N1-methyladenosine (m 1 A), 5-methylcytosine (m 5 C), 5-hydroxymethylcytosine (hm 5 C), pseudouridine (Ψ), inosine (I), uridine (U) and ribosemethylation (2'-O-Me). Most of these modifications contribute to pre-mRNA splicing, nuclear export, transcript stability and translation initiation in eukaryotic cells. By participating in various physiological processes, RNA modifications also have regulatory roles in the pathogenesis of tumour and non-tumour diseases. We discussed the physiological roles of RNA modifications and associated these roles with disease pathogenesis. Functioning as the bridge between transcription and translation, RNA modifications are vital for the progression of numerous diseases and can even regulate the fate of cancer cells.

The RNA methyltransferase NSUN6 suppresses pancreatic cancer development by regulating cell proliferation

“…Increasing evidences shown that RNA methyltransferases are aberrantly expressed and play critical roles in cancer development and pathogenesis [28 , 29] . Among these, N6-methyladenosine (m6A) is the best understood and frequent mark of mRNA, and the functions of which ranges from pre-mRNA processing, translation, miRNA biogenesis to mRNA decay [30] . The importance of METTL3 and ALKBH5 in the development and progression of pancreatic cancer have pointed out [31 , 32] .…”

RNA-based therapies: A cog in the wheel of lung cancer defense

“…RNA-based therapeutic strategies have emerged as an alternative to the conventional protein-based therapies that are difficult to pursue, as adapter proteins or transcription factors. These types of protein molecules can be regulated by modulating mRNA levels or translation of proteins [ 53 , 63 ]. The primary focus of oligonucleotide-based therapeutics includes gene silencing or activation and splice modulation that provides an extended range of potential targets beyond the conventionally accessible pharmacological strategies.…”

Context-Dependent Roles of RNA Modifications in Stress Responses and Diseases

“…The most abundant internal mRNA modification is N 6 -methyladenosine (m 6 A) [2]. Other mRNA modifications are reviewed elsewhere [2,3,12]. m 6 A writers include methyltransferase-like family members 3,14 (METTL3, METTL14), Wilms tumor 1-associated protein (WTAP), KIAA1429, RBM15/RBM15B, and Zc3h13 [2,13,14].…”