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Updated: Aug 4, 2025

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
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Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale

Published on: May 17, 2014

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Translation regulation of specific mRNAs by RPS26 C-terminal RNA-binding tail integrates energy metabolism and

Tal Havkin-Solomon1, Davide Fraticelli1, Anat Bahat1

  • 1Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 7610001, Israel.

Nucleic Acids Research
|April 4, 2023
PubMed

Insights

Ribosomal protein RPS26 directly binds mRNA, influencing translation initiation and conferring resistance to energy stress. This discovery highlights ribosome specialization in regulating gene expression during cellular stress.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Ribosome composition and modifications are known to influence translation control.
  • The role of direct mRNA binding by ribosomal proteins in regulating specific mRNA translation and ribosome specialization remains under-investigated.

Purpose of the Study:

  • To investigate the function of the RPS26 C-terminus in mRNA binding and translation regulation.
  • To explore the impact of RPS26 C-terminal mutations on cellular responses to energy stress.

Main Methods:

  • CRISPR-Cas9 gene editing was used to mutate the RPS26 C-terminus (RPS26dC).
  • Assays were performed to assess the effects of RPS26dC on translation initiation mediated by Kozak and TISU sequences.
  • Cellular responses to glucose starvation and mTOR inhibition were examined in RPS26dC cells.
  • Cellular signaling pathways (mTOR, AMPK) and translatome profiles were analyzed.

Main Results:

  • RPS26 C-terminal binding to 5'UTR sequences regulates translation initiation, with differential effects on Kozak and TISU motifs.
  • The RPS26dC mutation confers resistance to glucose starvation and mTOR inhibition.
  • RPS26dC cells exhibit reduced mTOR activity and activated AMP-activated protein kinase, mimicking energy-deprived wild-type cells.
  • The translatome of RPS26dC cells correlates with that of glucose-starved wild-type cells.

Conclusions:

  • The C-terminal region of RPS26 plays a crucial role in binding mRNA and regulating translation of specific mRNA features.
  • RPS26-mediated translation control is linked to cellular energy metabolism and stress response pathways.
  • Ribosome specialization, influenced by RPS26 RNA binding, contributes to the translation tolerance of TISU genes under energy stress.

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