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2'-O-methylation at internal sites on mRNA promotes mRNA stability.
Li, Yanqiang; Yi, Yang; Gao, Xinlei; Wang, Xin; Zhao, Dongyu; Wang, Rui; Zhang, Li-Sheng; Gao, Boyang; Zhang, Yadong; Zhang, Lili; Cao, Qi; Chen, Kaifu.
Afiliación
  • Li Y; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Yi Y; Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Gao X; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Wang X; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Zhao D; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Wang R; Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • Zhang LS; Department of Chemistry, Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong SAR, China; Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA; Howard Hughes Medical Institute, Chicago, IL, USA.
  • Gao B; Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA; Howard Hughes Medical Institute, Chicago, IL, USA.
  • Zhang Y; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Zhang L; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Cao Q; Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: qi.cao@northwestern.edu.
  • Chen K; Basic and Translational Research Division, Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Boston, MA, USA; Prostate Cancer Program, Dana-Farber/Harvard Cancer Center, Boston
Mol Cell ; 84(12): 2320-2336.e6, 2024 Jun 20.
Article en En | MEDLINE | ID: mdl-38906115
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Regiones no Traducidas 3' / Estabilidad del ARN Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ARN Mensajero / Regiones no Traducidas 3' / Estabilidad del ARN Límite: Humans Idioma: En Revista: Mol Cell Asunto de la revista: BIOLOGIA MOLECULAR Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos