2. Academic Validation
  3. DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1

DHX36 binding induces RNA structurome remodeling and regulates RNA abundance via m6A reader YTHDF1

  • Nat Commun. 2024 Nov 15;15(1):9890. doi: 10.1038/s41467-024-54000-y.
Yuwei Zhang # 1,  Jieyu Zhao # 2,  Xiaona Chen 3 4,  Yulong Qiao 3 4,  Jinjin Kang 5,  Xiaofan Guo 3 4,  Feng Yang 1,  Kaixin Lyu 2,  Yiliang Ding 6,  Yu Zhao 5,  Hao Sun 7,  Chun-Kit Kwok 8 9,  Huating Wang 10 11
Affiliations

Affiliations

  • 1 Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 2 Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong, SAR, China.
  • 3 Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, SAR, China.
  • 4 Center for Neuromusculoskeletal Restorative Medicine Limited, Hong Kong, SAR, China.
  • 5 Molecular Cancer Research Center, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
  • 6 Department of Cell and Developmental Biology, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, United Kingdom.
  • 7 Warshel Institute for Computational Biology, The Chinese University of Hong Kong, Shenzhen, China. sunhao100@cuhk.edu.cn.
  • 8 Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Hong Kong, SAR, China. ckkwok42@cityu.edu.hk.
  • 9 Shenzhen Research Institute of City University of Hong Kong, Shenzhen, China. ckkwok42@cityu.edu.hk.
  • 10 Department of Orthopaedics and Traumatology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, SAR, China. huating.wang@cuhk.edu.hk.
  • 11 Center for Neuromusculoskeletal Restorative Medicine Limited, Hong Kong, SAR, China. huating.wang@cuhk.edu.hk.
  • # Contributed equally.
PMID: 39543097 DOI: 10.1038/s41467-024-54000-y
Abstract

RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box helicase 36 (DHX36) is known to bind and unwind RNA G-quadruplex (rG4) structure but the transcriptome-wide RNA structure remodeling induced by DHX36 binding and the impact on RNA fate remain poorly understood. Here, we investigate the RNA structurome alteration induced by DHX36 depletion. Our findings reveal that DHX36 binding induces structural remodeling not only at the localized binding sites but also on the entire mRNA transcript most pronounced in 3'UTR regions. DHX36 binding increases structural accessibility at 3'UTRs which is correlated with decreased post-transcriptional mRNA abundance. Further analyses and experiments uncover that DHX36 binding sites are enriched for N6-methyladenosine (m6A) modification and YTHDF1 binding; and DHX36 induced structural changes may facilitate YTHDF1 binding to m6A sites leading to RNA degradation. Altogether, our findings uncover the structural remodeling effect of DHX36 binding and its impact on RNA abundance through regulating m6A dependent YTHDF1 binding.

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