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Pervasive downstream RNA hairpins dynamically dictate start-codon selection.
Xiang, Yezi; Huang, Wenze; Tan, Lianmei; Chen, Tianyuan; He, Yang; Irving, Patrick S; Weeks, Kevin M; Zhang, Qiangfeng Cliff; Dong, Xinnian.
Afiliação
  • Xiang Y; Department of Biology, Duke University, Durham, NC, USA.
  • Huang W; Howard Hughes Medical Institute, Duke University, Durham, NC, USA.
  • Tan L; MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China.
  • Chen T; Beijing Frontier Research Center for Biological Structures, Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, China.
  • He Y; Tsinghua-Peking Center for Life Sciences, Beijing, China.
  • Irving PS; Department of Pharmacology and Cancer Biology, Duke Medical Center, Duke University, Durham, NC, USA.
  • Weeks KM; Department of Biology, Duke University, Durham, NC, USA.
  • Zhang QC; Howard Hughes Medical Institute, Duke University, Durham, NC, USA.
  • Dong X; Department of Biology, Duke University, Durham, NC, USA.
Nature ; 621(7978): 423-430, 2023 Sep.
Article em En | MEDLINE | ID: mdl-37674078
Translational reprogramming allows organisms to adapt to changing conditions. Upstream start codons (uAUGs), which are prevalently present in mRNAs, have crucial roles in regulating translation by providing alternative translation start sites1-4. However, what determines this selective initiation of translation between conditions remains unclear. Here, by integrating transcriptome-wide translational and structural analyses during pattern-triggered immunity in Arabidopsis, we found that transcripts with immune-induced translation are enriched with upstream open reading frames (uORFs). Without infection, these uORFs are selectively translated owing to hairpins immediately downstream of uAUGs, presumably by slowing and engaging the scanning preinitiation complex. Modelling using deep learning provides unbiased support for these recognizable double-stranded RNA structures downstream of uAUGs (which we term uAUG-ds) being responsible for the selective translation of uAUGs, and allows the prediction and rational design of translating uAUG-ds. We found that uAUG-ds-mediated regulation can be generalized to human cells. Moreover, uAUG-ds-mediated start-codon selection is dynamically regulated. After immune challenge in plants, induced RNA helicases that are homologous to Ded1p in yeast and DDX3X in humans resolve these structures, allowing ribosomes to bypass uAUGs to translate downstream defence proteins. This study shows that mRNA structures dynamically regulate start-codon selection. The prevalence of this RNA structural feature and the conservation of RNA helicases across kingdoms suggest that mRNA structural remodelling is a general feature of translational reprogramming.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA de Cadeia Dupla / RNA Mensageiro / Códon de Iniciação / Conformação de Ácido Nucleico Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: RNA de Cadeia Dupla / RNA Mensageiro / Códon de Iniciação / Conformação de Ácido Nucleico Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article