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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
Published on: May 10, 2018
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JUN mRNA translation regulation is mediated by multiple 5' UTR and start codon features
Angélica M González-Sánchez1, Eimy A Castellanos-Silva2, Gabriela Díaz-Figueroa3
1Comparative Biochemistry Graduate Program, University of California, Berkeley, Berkeley, CA, United States of America.
Plos One
|March 14, 2024
Summary
JUN mRNA translation is complex, involving eukaryotic initiation factors (eIFs) like eIF3 and eIF4A. Regulation depends on sequence, structure, and upstream start codons, offering insights into cellular control mechanisms.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Eukaryotic initiation factors (eIFs) regulate mRNA translation, essential for cell survival.
- The JUN mRNA, encoding the oncogenic transcription factor JUN, is stimulated by eIF3 via interactions with its 5' UTR and cap structure.
- The JUN 5' UTR is extensive, with significant secondary structure, high GC content, and an upstream start codon (uAUG), suggesting complex regulation.
Purpose of the Study:
- To investigate the intricate regulation of JUN mRNA translation in human cells.
- To identify sequence- and structure-dependent regulatory elements within the JUN 5' UTR.
- To explore the roles of additional initiation factors, specifically eIF4A, in JUN mRNA regulation.
Main Methods:
- Analysis of JUN mRNA translation regulation in human cells.
- Investigating the impact of eIF4A interaction with JUN mRNA using Rocaglamide A (RocA).
- Examining the contribution of upstream (uAUG) and main (mAUG) start codons to JUN translation.
Main Results:
- JUN translation is regulated in a sequence- and structure-dependent manner within the JUN 5' UTR, near the eIF3-binding site.
- Enhancing eIF4A interaction with JUN mRNA via RocA treatment represses JUN translation.
- Both uAUG and mAUG are conserved in vertebrates and contribute to JUN translation.
Conclusions:
- JUN mRNA translation involves multiple, interacting regulatory layers beyond known eIF3 interactions.
- eIF4A plays a significant role in JUN mRNA translation, with its interaction modulated by RocA.
- JUN mRNA serves as a valuable model for understanding complex, multi-faceted mRNA translation regulation.
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