m6A RNA Methylation Controls Neural Development and Is Involved in Human Diseases

Abstract

RNA modifications are involved in many aspects of biological functions. N6-methyladenosine (m⁶A) is one of the most important forms of RNA methylation and plays a vital role in regulating gene expression, protein translation, cell behaviors, and physiological conditions in many species, including humans. The dynamic and reversible modification of m⁶A is conducted by three elements: methyltransferases ("writers"), such as methyltransferase-like protein 3 (METTL3) and METTL14; m⁶A-binding proteins ("readers"), such as the YTH domain family proteins (YTHDFs) and YTH domain-containing protein 1 (YTHDC1); and demethylases ("erasers"), such as fat mass and obesity-associated protein (FTO) and AlkB homolog 5 (ALKBH5). In this review, we summarize the current knowledge on mapping mRNA positions of m⁶A modification and revealing molecular processes of m⁶A. We further highlight the biological significance of m⁶A modification in neural cells during development of the nervous system and its association with human diseases. m⁶A RNA methylation is becoming a new frontier in neuroscience and should help us better understand neural development and neurological diseases from a novel point of view.

Keywords: Demethylase; FTO; METTL3; Methyltransferase; N6-methyladenosine (m6A); Neural development.