Authors |
Li X, Xiong X, Zhang M, Wang K, Chen Y, Zhou J, Mao Y, Lv J, Yi D, Chen XW, Wang C, Qian SB, Yi C |
Abstract |
Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N 1 -methyladenosine (m 1 A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m 1 A profiling method, based on m 1 A-induced misincorporation during reverse transcription, and report distinct classes of m 1 A methylome in the human transcriptome. m 1 A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency. A different, small subset of m 1 A exhibit a GUUCRA tRNA-like motif, are evenly distributed in the transcriptome, and are dependent on the methyltransferase TRMT6/61A. Additionally, we show that m 1 A is prevalent in the mitochondrial-encoded transcripts. Manipulation of m 1 A level via TRMT61B, a mitochondria-localizing m 1 A methyltransferase, demonstrates that m 1 A in mitochondrial mRNA interferes with translation. Collectively, our approaches reveal distinct classes of m 1 A methylome and provide a resource for functional studies of m 1 A-mediated epitranscriptomic regulation. Copyright © 2017 Elsevier Inc. All rights reserved. |