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Updated: Jan 14, 2026

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De novo Identification of Actively Translated Open Reading Frames with Ribosome Profiling Data
Published on: February 18, 2022
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Pan-modification profiling facilitates a cross-evolutionary dissection of the thermoregulated ribosomal
Miguel A Garcia-Campos1, Joe Georgeson1, Ronit Nir1
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Cell
|October 23, 2025
Summary
New Pan-Mod-seq technology reveals dynamic ribosomal RNA modifications in extreme heat-loving organisms. These modifications enhance ribosome stability and are crucial for growth under high temperatures.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Ribosomal RNA (rRNA) is central to ribosome structure and function.
- Chemical modifications of rRNA are widespread but challenging to study systematically.
- Understanding rRNA modification dynamics is crucial for cell biology.
Purpose of the Study:
- To develop a method for high-throughput analysis of rRNA modifications.
- To investigate the plasticity and dynamics of rRNA modifications across diverse life forms.
- To elucidate the role of specific modifications in thermal adaptation.
Main Methods:
- Development of Pan-Mod-seq for parallel inference of 16 distinct rRNA modifications.
- Application of Pan-Mod-seq to 14 species across all domains of life.
- Cryo-electron microscopy (cryo-EM) and biophysical studies to determine structural and functional roles.
Main Results:
- Pan-Mod-seq enables parallel analysis of numerous rRNA modifications.
- Extreme hyperthermophiles exhibit dynamic rRNA modifications (∼50%), unlike mesophiles.
- A conserved module of m5C-ac4C modifications, induced by heat, stabilizes ribosomes and is essential for growth at high temperatures.
Conclusions:
- rRNA modification plasticity varies significantly with environmental conditions, particularly temperature.
- Specific rRNA modifications play a critical role in conferring thermostability to ribosomes.
- This work provides a foundation for studying the rRNA epitranscriptome in various biological contexts, including health and disease.
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