RNA m6A modification and its function in diseases

Abstract

N⁶-methyladenosine (m⁶A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism. m⁶A modification could be installed by m⁶A "writers" composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m⁶A "erasers" (FTO and ALKBH5). The function of m⁶A is executed by m⁶A "readers" that bind to m⁶A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in m⁶A modulators ("writers," "erasers," and "readers") have remarkably renewed our understanding of the function and regulation of m⁶A in different cells under normal or disease conditions. However, the mechanism and the regulatory network of m⁶A are still largely unknown. Moreover, investigations of the m⁶A physiological roles in human diseases are limited. In this review, we summarize the recent advances in m⁶A research and highlight the functional relevance and importance of m⁶A modification in in vitro cell lines, in physiological contexts, and in cancers.

Keywords: RNA modification; cancer; epigenetics; immunity; m6A.