M6A-express: uncovering complex and condition-specific m6A regulation of gene expression. Issue 20 (20th August 2021)

• Record Type: Journal Article
• Authors: Zhang, Teng; Zhang, Shao-Wu; Zhang, Song-Yao; Gao, Shou-Jiang; Chen, Yidong; Huang, Yufei
• Is Part Of: Nucleic acids research. Volume 49:Issue 20(2021)
• Page Start: e116
• Page End: e116
• Publication Date: 2021-08-20
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkab714
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: N 6 -methyladenosine (m 6 A) is the most abundant form of mRNA modification and controls many aspects of RNA metabolism including gene expression. However, the mechanisms by which m 6 A regulates cell- and condition-specific gene expression are still poorly understood, partly due to a lack of tools capable of identifying m 6 A sites that regulate gene expression under different conditions. Here we develop m 6 A-express, the first algorithm for predicting condition-specific m 6 A regulation of gene expression (m 6 A-reg-exp) from limited methylated RNA immunoprecipitation sequencing (MeRIP-seq) data. Comprehensive evaluations of m 6 A-express using simulated and real data demonstrated its high prediction specificity and sensitivity. When only a few MeRIP-seq samples may be available for the cellular or treatment conditions, m 6 A-express is particularly more robust than the log-linear model. Using m 6 A-express, we reported that m 6 A writers, METTL3 and METTL14, competitively regulate the transcriptional processes by mediating m 6 A-reg-exp of different genes in Hela cells. In contrast, METTL3 induces different m 6 A-reg-exp of a distinct group of genes in HepG2 cells to regulate protein functions and stress-related processes. We further uncovered unique m 6 A-reg-exp patterns in human brain and intestine tissues, which are enriched in organ-specific processes. This study demonstrates the effectiveness of m 6 A-express in predicting condition-specific m 6 A-reg-exp and highlights the complex, condition-specific nature of m 6 A-regulation of gene expression.