Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/145157
Title: METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing
Authors: Goh, Yeek Teck
Koh, Casslynn W. Q.
Sim, Donald Yuhui
Roca, Xavier
Goh, W. S. Sho
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Goh, Y. T., Koh, C. W. Q., Sim, D. Y., Roca, X., & Goh, W. S. S. (2020). METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing. Nucleic Acids Research, 48(16), 9250-9261. doi:10.1093/nar/gkaa684
Project: 1610151037
MOE2016-T2-2-104(S)
RG33/15
Journal: Nucleic Acids Research
Abstract: N6-methylation of 2′-O-methyladenosine (Am) in RNA occurs in eukaryotic cells to generate N6,2′-O-dimethyladenosine (m6Am). Identification of the methyltransferase responsible for m6Am catalysis has accelerated studies on the function of m6Am in RNA processing. While m6Am is generally found in the first transcribed nucleotide of mRNAs, the modification is also found internally within U2 snRNA. However, the writer required for catalyzing internal m6Am formation had remained elusive. By sequencing transcriptome-wide RNA methylation at single-base-resolution, we identified human METTL4 as the writer that directly methylates Am at U2 snRNA position 30 into m6Am. We found that METTL4 localizes to the nucleus and its conserved methyltransferase catalytic site is required for U2 snRNA methylation. By sequencing human cells with overexpressed Mettl4, we determined METTL4’s in vivo target RNA motif specificity. In the absence of Mettl4 in human cells, U2 snRNA lacks m6Am thereby affecting a subset of splicing events that exhibit specific features such as 3′ splice-site weakness and an increase in exon inclusion. These findings suggest that METTL4 methylation of U2 snRNA regulates splicing of specific pre-mRNA transcripts.
URI: https://hdl.handle.net/10356/145157
ISSN: 0305-1048
DOI: 10.1093/nar/gkaa684
Rights: © 2020 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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