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Updated: Jul 5, 2025
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
Transcriptional profile of ribosome-associated quality control components and their associated phenotypes in
Otávio Augusto Leitão Dos Santos1, Rodolfo L Carneiro1, Rodrigo D Requião2
1Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
Abstract:
During protein synthesis, organisms detect translation defects that induce ribosome stalling and result in protein aggregation. The Ribosome-associated Quality Control (RQC) complex, comprising TCF25, LTN1, and NEMF, is responsible for identifying incomplete protein products from unproductive translation events, targeting them for degradation. Although RQC disruption causes adverse effects on vertebrate neurons, data regarding mRNA/protein expression and regulation across tissues are lacking. Employing high-throughput methods, we analyzed public datasets to explore RQC gene expression and phenotypes. Our findings revealed widespread expression of RQC components in human tissues; however, silencing of RQC yielded only mild negative effects on cell growth. Notably, TCF25 exhibited elevated mRNA levels that were not reflected in the protein content. We experimentally demonstrated that this disparity arose from post-translational protein degradation by the proteasome. Additionally, we observed that cellular aging marginally influenced RQC expression, leading to reduced mRNA levels in specific tissues. Our results suggest the necessity of RQC expression in all mammalian tissues. Nevertheless, when RQC falters, alternative mechanisms seem to compensate, ensuring cell survival under nonstress conditions.
Insights
The Ribosome-associated Quality Control (RQC) complex is vital for protein synthesis quality control across all mammalian tissues. Despite its importance, cells can survive mild RQC disruptions due to compensatory mechanisms.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Protein synthesis defects trigger ribosome stalling and protein aggregation.
- The Ribosome-associated Quality Control (RQC) complex (TCF25, LTN1, NEMF) targets aberrant proteins for degradation.
- RQC disruption impacts vertebrate neurons, but tissue-specific expression and regulation remain unclear.
Purpose of the Study:
- To investigate the expression patterns and regulatory mechanisms of RQC components across human tissues.
- To assess the impact of RQC gene silencing on cellular phenotypes.
- To explore the relationship between RQC expression and cellular aging.
Main Methods:
- Analysis of public high-throughput datasets for RQC gene expression and associated phenotypes.
- Experimental validation of mRNA-protein level discrepancies for TCF25.
- Investigation of proteasomal degradation pathways.
- Assessment of RQC expression changes during cellular aging.
Main Results:
- Widespread expression of RQC components found across human tissues.
- RQC silencing resulted in only minor negative effects on cell growth.
- TCF25 mRNA levels were elevated, but protein levels were not, due to proteasomal degradation.
- Cellular aging led to marginal decreases in RQC mRNA levels in certain tissues.
Conclusions:
- RQC expression is essential in all mammalian tissues.
- Alternative cellular mechanisms compensate for RQC dysfunction under non-stress conditions.
- Post-translational regulation, specifically proteasomal degradation, plays a key role in controlling TCF25 protein levels.
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