Dynamic landscape and evolution of m6A methylation in human

Abstract

m6A is a prevalent internal modification in mRNAs and has been linked to the diverse effects on mRNA fate. To explore the landscape and evolution of human m6A, we generated 27 m6A methylomes across major adult tissues. These data reveal dynamic m6A methylation across tissue types, uncover both broadly or tissue-specifically methylated sites, and identify an unexpected enrichment of m6A methylation at non-canonical cleavage sites. A comparison of fetal and adult m6A methylomes reveals that m6A preferentially occupies CDS regions in fetal tissues. Moreover, the m6A sub-motifs vary between fetal and adult tissues or across tissue types. From the evolutionary perspective, we uncover that the selection pressure on m6A sites varies and depends on their genic locations. Unexpectedly, we found that ∼40% of the 3′UTR m6A sites are under negative selection, which is higher than the evolutionary constraint on miRNA binding sites, and much higher than that on A-to-I RNA modification. Moreover, the recently gained m6A sites in human populations are clearly under positive selection and associated with traits or diseases. Our work provides a resource of human m6A profile for future studies of m6A functions, and suggests a role of m6A modification in human evolutionary adaptation and disease susceptibility.

Regulation of RNA N6-methyladenosine modification and its emerging roles in skeletal muscle development

“…To date, a few studies have evaluated the genome-wide m 6 A modification on skeletal muscle tissue in vivo, the dynamic change of m 6 A methylation in skeletal muscle development and the correlation between m 6 A and skeletal muscle are explored [14,103,110]. Many muscle-specific m 6 A sites have been identified in mammals [41,110,111]. In mouse, it's reported that the maternal high-fat diet alters the m 6 A pattern in skeletal muscle and adipose in a development-dependent way [112].…”

Multifaceted Functions and Novel Insight Into the Regulatory Role of RNA N6-Methyladenosine Modification in Musculoskeletal Disorders

“…As aforementioned, m 6 A modification is a dynamic and reversible epigenetic change ( Zhang et al, 2020 ), which affects the stability and function of RNAs, thereby modulating the pathogenesis and progression of diseases ( Qin et al, 2020 ; Wang et al, 2020 ; Zhu et al, 2020 ). M 6 A modification has been identified in more than 7,000 human genes, and it preferentially occurred at the site of stop codons and long internal exons within the RRACH sequence (R = G or A; H = A, C, or U) ( Dominissini et al, 2012 ).…”

Dynamic Expression of m6A Regulators During Multiple Human Tissue Development and Cancers

“…Xia et al had generated 21 whole transcriptome m 6 A methylomes across major fetal tissues (Xiao et al, 2019 ); however, no adult tissues were included. Moreover, Zhang et al generated 27 m 6 A methylomes across major adult tissues (Zhang et al, 2020a ). Besides of protein coding genes, noncoding RNAs have been found to play important roles in development and cancer (Li et al, 2020 ; Xu et al, 2020a ; Zhang et al, 2020b ).…”