FTO controls reversible m6Am RNA methylation during snRNA biogenesis

J Mauer, M Sindelar, V Despic, T Guez… - Nature chemical …, 2019 - nature.com
J Mauer, M Sindelar, V Despic, T Guez, BR Hawley, JJ Vasseur, A Rentmeister, SS Gross…
Nature chemical biology, 2019nature.com
Small nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA
splicing. Here we show that snRNAs contain a regulated and reversible nucleotide
modification causing them to exist as two different methyl isoforms, m1 and m2, reflecting the
methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA
biogenesis involves the formation of an initial m1 isoform with a single-methylated
adenosine (2′-O-methyladenosine, Am), which is then converted to a dimethylated m2 …
Abstract
Small nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. Here we show that snRNAs contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m1 and m2, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m1 isoform with a single-methylated adenosine (2′-O-methyladenosine, Am), which is then converted to a dimethylated m2 isoform (N6,2′-O-dimethyladenosine, m6Am). The relative m1 and m2 isoform levels are determined by the RNA demethylase FTO, which selectively demethylates the m2 isoform. We show FTO is inhibited by the oncometabolite d-2-hydroxyglutarate, resulting in increased m2-snRNA levels. Furthermore, cells that exhibit high m2-snRNA levels show altered patterns of alternative splicing. Together, these data reveal that FTO controls a previously unknown central step of snRNA processing involving reversible methylation, and suggest that epitranscriptomic information in snRNA may influence mRNA splicing.
nature.com
以上显示的是最相近的搜索结果。 查看全部搜索结果