%0 Journal Article
%T 2'-O-methylation at internal sites on mRNA promotes mRNA stability.
%A Li Y
%A Yi Y
%A Gao X
%A Wang X
%A Zhao D
%A Wang R
%A Zhang LS
%A Gao B
%A Zhang Y
%A Zhang L
%A Cao Q
%A Chen K
%J Mol Cell
%V 84
%N 12
%D 2024 Jun 20
%M 38906115
%F 19.328
%R 10.1016/j.molcel.2024.04.011
%X 2'-O-methylation (Nm) is a prominent RNA modification well known in noncoding RNAs and more recently also found at many mRNA internal sites. However, their function and base-resolution stoichiometry remain underexplored. Here, we investigate the transcriptome-wide effect of internal site Nm on mRNA stability. Combining nanopore sequencing with our developed machine learning method, NanoNm, we identify thousands of Nm sites on mRNAs with a single-base resolution. We observe a positive effect of FBL-mediated Nm modification on mRNA stability and expression level. Elevated FBL expression in cancer cells is associated with increased expression levels for 2'-O-methylated mRNAs of cancer pathways, implying the role of FBL in post-transcriptional regulation. Lastly, we find that FBL-mediated 2'-O-methylation connects to widespread 3' UTR shortening, a mechanism that globally increases RNA stability. Collectively, we demonstrate that FBL-mediated Nm modifications at mRNA internal sites regulate gene expression by enhancing mRNA stability.