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Peer-reviewedCC BYScience Advances

DeCoRE: A computational method to resolve RNA structural heterogeneity from RNA structure probing data by direct RNA sequencing

  • Yong Huang1,2
  • Jinsong Zhang1
  • Lei Sun3,4
  • Qiangfeng Cliff Zhang1
4 affiliations
  1. 1State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Tsinghua-Peking Center for Life Sciences, Center for Life Sciences and Artificial intelligence, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  2. 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China.
  3. 3Shandong Provincial Key Laboratory of Animal Cell and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China.
  4. 4State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
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Abstract

RNA molecules are inherently dynamic, forming complex structural ensembles of alternative conformations that direct their cellular functions. Current methods for resolving RNA structural heterogeneity and dynamics have been developed for short-read sequencing-based structure probing, limiting their sensitivity and resolution. Here, we introduce DeCoRE (deconvolving complex RNA structural ensembles), a computational method that leverages direct RNA sequencing to resolve RNA structural heterogeneity and dynamics at the individual transcript level. DeCoRE combines enhanced structural signal detection with direct clustering of sequencing reads to sensitively deconvolve RNA structural ensembles at single-nucleotide resolution. We demonstrate DeCoRE's capabilities by resolving the known alternative conformations of the lysine and TPP riboswitches and uncover a previously uncharacterized cotranscriptional folding pathway of bacterial ribosomal RNA, where two conformations coexist during early elongation and progressively converge into a single mature conformation. DeCoRE represents a powerful tool for dissecting RNA structural heterogeneity and dynamics, advancing our understanding of RNA function.

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Cite

BibTeXRIS
BibTeX
@article{huang2026decore,
  title = {{DeCoRE: A computational method to resolve RNA structural heterogeneity from RNA structure probing data by direct RNA sequencing}},
  author = {Yong Huang and Jinsong Zhang and Lei Sun and Qiangfeng Cliff Zhang},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aef0670},
  url = {https://www.science.org/doi/10.1126/sciadv.aef0670},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - DeCoRE: A computational method to resolve RNA structural heterogeneity from RNA structure probing data by direct RNA sequencing
AU  - Yong Huang
AU  - Jinsong Zhang
AU  - Lei Sun
AU  - Qiangfeng Cliff Zhang
PY  - 2026
DA  - 2026/10/02
JO  - Science Advances
DO  - 10.1126/sciadv.aef0670
UR  - https://www.science.org/doi/10.1126/sciadv.aef0670
AB  - RNA molecules are inherently dynamic, forming complex structural ensembles of alternative conformations that direct their cellular functions. Current methods for resolving RNA structural heterogeneity and dynamics have been developed for short-read sequencing-based structure probing, limiting their sensitivity and resolution. Here, we introduce DeCoRE (deconvolving complex RNA structural ensembles), a computational method that leverages direct RNA sequencing to resolve RNA structural heterogeneity and dynamics at the individual transcript level. DeCoRE combines enhanced structural signal detection with direct clustering of sequencing reads to sensitively deconvolve RNA structural ensembles at single-nucleotide resolution. We demonstrate DeCoRE's capabilities by resolving the known alternative conformations of the lysine and TPP riboswitches and uncover a previously uncharacterized cotranscriptional folding pathway of bacterial ribosomal RNA, where two conformations coexist during early elongation and progressively converge into a single mature conformation. DeCoRE represents a powerful tool for dissecting RNA structural heterogeneity and dynamics, advancing our understanding of RNA function.
SN  - 2375-2548
ER  -