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April 23, 2026Nucleic Acids ResearchOpen Access

Multimodal profiling reveals cell type-specific pseudouridine modification and density-dependent translational regulation

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Authors

CMCaroline A. McCormickMMMichele MeseonznikYQYuchen Qiu

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Overview

Multimodal profiling shows translational effects of pseudouridine in human cell lines, suggesting its role in protein production.

Key Points

  • This research investigates how pseudouridine modifications affect translation and protein production across cell types.
  • Used direct RNA nanopore sequencing to map pseudouridine at single-nucleotide resolution in six human cell lines.
  • Integrated pseudouridine maps with proteomic and ribosome profiling datasets for comprehensive analysis.
  • Conducted TRUB1 knockout experiments to assess the impact of pseudouridine on protein abundance.
  • Identified that conserved pseudouridine sites enhance protein production when installed by TRUB1.
  • Demonstrated a paradox where clustered pseudouridine sites reduced protein abundance despite higher translation efficiency.
  • Confirmed that increased pseudouridine density negatively affects protein output in controlled in vitro translation experiments.

Cite This Study

McCormick et al. (2026) studied this question.

synapsesocial.com/papers/69e9ba6b85696592c86eca78https://doi.org/10.1093/nar/gkag353
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