Related Experiment Video
Updated: Jun 7, 2025
06:58
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
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LARP1 binds ribosomes and TOP mRNAs in repressed complexes
James A Saba1,2, Zixuan Huang3, Kate L Schole1,2
1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
The EMBO Journal
|November 12, 2024
Summary
LARP1 directly binds ribosomal subunits, not translating ribosomes, to regulate ribosomal protein mRNAs (TOPs). This challenges current models of LARP1-mediated TOP repression and stabilization.
Area of Science:
- Molecular Biology
- Structural Biology
- Cell Biology
Background:
- Terminal oligopyrimidine motif-containing mRNAs (TOPs) encode ribosomal proteins and are crucial for regulating ribosome synthesis.
- LARP1 has been implicated in repressing and stabilizing TOPs through interactions with 40S- or 80S-ribosome complexes, but the molecular mechanisms are unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms by which LARP1 interacts with ribosomal subunits and TOP mRNAs.
- To investigate the role of LARP1-ribosome complexes in TOP mRNA regulation.
Main Methods:
- Cryo-electron microscopy (Cryo-EM) to determine the structure of LARP1-ribosome complexes.
- Biochemical assays to study LARP1 binding to ribosomal subunits and TOPs.
Main Results:
- LARP1 directly binds to non-translating 40S ribosomal subunits via a novel domain, occluding the mRNA channel.
- LARP1 forms 80S complexes with TOPs upon increased availability of free ribosomal subunits during stress.
- Ribosome binding is not essential for LARP1's known functions in TOP repression and stabilization.
Conclusions:
- LARP1 directly binds ribosomal subunits, offering a new perspective on its regulatory role.
- Existing models of LARP1-mediated TOP regulation via repressed 40S/80S-TOP complexes need revision.
- This study provides critical molecular insights into LARP1-ribosome interactions and TOP mRNA regulation.
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