The dynamic N1-methyladenosine methylome in eukaryotic messenger RNA

By D. Dominissini, S. Nachtergaele, S. Moshitch-Moshkovitz, Eyal Peer, N. Kol, Moshe Shay Ben-Haim, Qing Dai, A. Di Segni, M. Salmon-Divon, Wesley C. Clark and 10 more. Nature, 2016

878 citations recorded by the source corpus.

Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6-methyladenosine (m6A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m1A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m1A in promoting translation of methylated mRNA.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/86df61772fa7aa7ec7f6eb43704d602773dc6f82

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Citations in the corpus

Critical Roles of N6-Methyladenosine (m6A) in Cancer and Virus Infection (2020, background): “Moreover, mRNA modifications are distributed in a position-specific manner; for example, m1A occurs near translation start codons and first splice sites, whereas m6A enriches in long coding sequences and the 3′-UTR [9,10,16,17], which is a regulatory element for mRNA, where miRNA and other proteins ”
The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution (2017, methodology): “We hence used a chi-squared test on the basis of the aggregated misincorporation counts (across replicates), to test the hypotheses that (1) the number of mismatches in the IP sample is higher than Input, and (2) the number of mismatches in IP is higher than in IP+Dimroth.”
YTH Domain: A Family of N6-methyladenosine (m6A) Readers (2018, background): “Are there more proteins that recognize m(6)A directly? How should we go about discovering the reader proteins of many other RNA modifications, such as the N(1)methyladenosine (m(1)A) [65], 5-methylcytosine (m(5)C) [66], N6,20-O-dimethyladenosine (m(6)Am) [67], and pseudouridine (w) [68]? Could a bet”