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Translation elongation rate varies among organs and decreases with age

Maxim V Gerashchenko1, Zalan Peterfi1, Sun Hee Yim1

  • 1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Nucleic Acids Research
|December 2, 2020
PubMed

Insights

Scientists developed a new method to measure protein synthesis rates in live animals. This technique reveals significant differences in translation elongation rates across organs and with aging.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Physiology

Background:

  • Targeting protein synthesis is a key strategy for disease treatment and lifespan extension.
  • Assessing translation in live animals is challenging due to biological complexity.
  • Existing methods limit monitoring and manipulation within organs and cells.

Purpose of the Study:

  • To develop a novel, labeling-free method for measuring organ- and cell-type-specific translation elongation rates in vivo.
  • To enable detailed analysis of protein synthesis regulation in complex biological systems.
  • To investigate how translation elongation varies across different tissues and with age.

Main Methods:

  • Developed a method involving time-resolved delivery of translation inhibitors (initiation and elongation) in live animals.
  • Utilized ribosome profiling to analyze translation dynamics.
  • Enabled organ-specific reporting of translation initiation sites.

Main Results:

  • Demonstrated significant organ-specific differences in translation elongation rates, exceeding 50%.
  • Quantified elongation rates: 6.8 aa/sec (liver), 5.0 aa/sec (kidney), 4.3 aa/sec (skeletal muscle).
  • Observed a 20% reduction in elongation rate between young adulthood and mid-life.

Conclusions:

  • Translation elongation is tightly regulated, varying significantly across mouse organs.
  • Age-related decline in translation elongation suggests a role in aging processes.
  • The developed method provides a powerful tool for studying in vivo translation dynamics.

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