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Updated: Jun 9, 2026

Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions
10:52

Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions

Published on: September 28, 2017

Structure-driven RNA remodeling underlies broad substrate recognition by NSUN2.

Qian Hu1, Wen Yang1, Yunyun Yu1

  • 1Department of Clinical Laboratory, Center for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.

Science China. Life Sciences
|June 8, 2026
PubMed
Summary

The human RNA methyltransferase NSUN2 uses a structure-first approach to modify cytosine on various RNA molecules. This mechanism allows NSUN2 to recognize diverse RNA substrates while maintaining catalytic specificity.

Keywords:
NSUN2conformational remodelingcryo-EMm5C modificationsubstrate recognitiontRNA methyltransferase

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Last Updated: Jun 9, 2026

Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions
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Nanomanipulation of Single RNA Molecules by Optical Tweezers
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Published on: August 20, 2014

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • NSUN2 is a human RNA methyltransferase catalyzing m5C modification.
  • NSUN2 regulates diverse biological processes by modifying RNA.
  • The mechanism of NSUN2's substrate recognition and catalytic specificity was unclear.

Purpose of the Study:

  • To elucidate the molecular basis of NSUN2's broad substrate recognition and catalytic specificity.
  • To determine the structures of NSUN2 in substrate-free and substrate-bound states.

Main Methods:

  • X-ray crystallography
  • Cryo-electron microscopy (cryo-EM)
  • Structural analysis of NSUN2-tRNA complexes

Main Results:

  • NSUN2 employs a structure-first, sequence-tolerant strategy.
  • NSUN2 actively remodels RNA architecture to expose the target cytosine.
  • A conserved interaction interface accommodates diverse tRNA substrates.

Conclusions:

  • NSUN2 achieves substrate specificity through structural remodeling rather than sequence recognition.
  • The findings define the molecular principles of NSUN2-mediated RNA m5C modification.