m6A reader proteins: the executive factors in modulating viral replication and host immune response

Abstract

N6-Methyladenosine (m6A) modification is the most abundant covalent modification of RNA. It is a reversible and dynamic process induced by various cellular stresses including viral infection. Many m6A methylations have been discovered, including on the genome of RNA viruses and on RNA transcripts of DNA viruses, and these methylations play a positive or negative role on the viral life cycle depending on the viral species. The m6A machinery, including the writer, eraser, and reader proteins, achieves its gene regulatory role by functioning in an orchestrated manner. Notably, data suggest that the biological effects of m6A on target mRNAs predominantly depend on the recognition and binding of different m6A readers. These readers include, but are not limited to, the YT521-B homology (YTH) domain family, heterogeneous nuclear ribonucleoproteins (HNRNPs), insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs), and many others discovered recently. Indeed, m6A readers have been recognized not only as regulators of RNA metabolism but also as participants in a variety of biological processes, although some of these reported roles are still controversial. Here, we will summarize the recent advances in the discovery, classification, and functional characterization of m6A reader proteins, particularly focusing on their roles and mechanisms of action in RNA metabolism, gene expression, and viral replication. In addition, we also briefly discuss the m6A-associated host immune responses in viral infection.

Research Advances in the Roles of N6-Methyladenosine Modification in Ovarian Cancer

“…For example, HNRNPC and HNRNPG preferentially bind to m6A-modified RNAs through an “m6A-switch” mechanism. 64 HNRNPA2B1 is highly expressed in OC tissues, garnering attention for its role as an oncogene in OC development. Chen et al identified HNRNPA2B1 as a potential target of miR-30c-5p in OC.…”

Nurturing gut health: role of m6A RNA methylation in upholding the intestinal barrier

“…This dysfunction manifests as changes in gut microbiota diversity and abundance, increased intestinal mucosal permeability, and compromised immune responses [4][5][6][7]. Notably, fluctuations in N6methyladenosine (m6A) modification levels have also been observed in these conditions [8][9][10]. m6A modification, a prevalent internal RNA chemical modification involving the methylation of adenosine at the N6 site, has emerged as a key player in regulating intestinal homeostasis [11].…”