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Related Experiment Videos

Changes in translational yield regulate tissue-specific expression of beta-glucuronidase.

L T Bracey1, K Paigen

  • 1University of California, Berkeley 94720.

Proceedings of the National Academy of Sciences of the United States of America
|December 1, 1987
PubMed
Summary

Tissue differences in beta-glucuronidase (GUS) levels are mainly due to synthesis rates, not degradation. Translational yield, a measure of protein synthesis efficiency, significantly impacts GUS gene regulation across mouse tissues.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Beta-glucuronidase (GUS) enzyme levels vary significantly across different mouse tissues.
  • Understanding the regulatory mechanisms behind these variations is crucial for comprehending gene expression.
  • Previous studies often focused on transcriptional regulation or mRNA stability for housekeeping genes.

Purpose of the Study:

  • To investigate the regulatory mechanisms responsible for the 12-fold variation in beta-glucuronidase (GUS) molecules per cell among mouse tissues.
  • To determine the relative contributions of protein synthesis and degradation rates to tissue-specific GUS levels.
  • To explore the role of translational yield in differential gene regulation.

Main Methods:

  • Quantification of GUS protein synthesis (ks) and degradation (kd) rates in six different mouse tissues.

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  • Measurement of GUS mRNA levels per cell in these tissues.
  • Experimental estimation of translational yield, defined as the efficiency of mRNA translation and polypeptide maturation.

    • Main Results:

    • Differences in GUS enzyme levels among tissues were primarily driven by variations in protein synthesis rates (ks).
    • Protein degradation rates (kd) showed significant differences only in the brain.
    • Observed differences in GUS mRNA levels were insufficient to explain the variations in synthesis rates, implicating translational yield.
    • Experimental validation confirmed that translational yield is a significant factor in tissue-specific GUS gene regulation for both N and B haplotypes.

    Conclusions:

    • Translational yield, an aspect of protein synthesis, serves as a key differential regulatory mechanism for GUS gene expression across mouse tissues.
    • Unlike special-function genes regulated transcriptionally, housekeeping genes like GUS can be differentially regulated at the translational level.
    • This study highlights translational yield as an important, previously underestimated, regulatory mechanism in gene expression.