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Deciphering the Dynamic Landscape of Transcription-Associated mRNP Quality Control Components Over the Whole Yeast
Kévin Moreau1, Aurélia Le Dantec1, A Rachid Rahmouni2
1Centre de Biophysique Moléculaire, UPR 4301 du CNRS, Orléans, France.
Abstract:
In eukaryotic cells, aberrant mRNPs with processing and packaging defects are targeted co-transcriptionally by a surveillance system that triggers their nuclear retention and ultimately the degradation of their mRNA component by the 3'-5' activity of the exosome-associated exonuclease Rrp6. This mRNP quality control process is stimulated by the NNS complex (Nrd1-Nab3-Sen1), which otherwise mediates termination, processing, and decay of ncRNAs. The process involves also the exosome co-activator TRAMP complex (Trf4-Air2-Mtr4). Here, we describe a genome-wide approach to visualize the dynamic movement and coordination of these quality control components over the yeast chromosomes upon perturbation of mRNP biogenesis. The method provides valuable information on how the surveillance system is precisely coordinated both physically and functionally with the transcription machinery to detect the faulty events during perturbation of mRNP biogenesis. The overview shows also that the gathering of the quality control components over affected mRNA genes takes place at the expense of their commitment to be recruited at ncRNA genomic features, provoking termination and processing defects of ncRNAs.
Insights
Eukaryotic cells use a surveillance system to degrade faulty messenger RNAs (mRNAs). This system, involving the NNS complex and TRAMP, coordinates with transcription to ensure mRNA quality control.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Eukaryotic cells possess a quality control system to identify and degrade aberrant messenger ribonucleoprotein complexes (mRNPs) with processing and packaging defects.
- This surveillance mechanism, involving the NNS complex (Nrd1-Nab3-Sen1) and TRAMP complex (Trf4-Air2-Mtr4), targets defective mRNAs for degradation by the exosome-associated exonuclease Rrp6.
- The NNS complex also plays a role in the termination, processing, and decay of non-coding RNAs (ncRNAs).
Purpose of the Study:
- To visualize the dynamic movement and coordination of mRNP quality control components across yeast chromosomes.
- To understand how the surveillance system physically and functionally interacts with the transcription machinery during perturbations of mRNP biogenesis.
- To investigate the impact of mRNP quality control on ncRNA processing and termination.
Main Methods:
- Developed a genome-wide approach to visualize the dynamic movement of quality control factors.
- Perturbed mRNP biogenesis to study the surveillance system's response.
- Monitored the recruitment of NNS and TRAMP complexes to mRNA and ncRNA genes.
Main Results:
- Demonstrated the dynamic recruitment of quality control components to specific genomic locations.
- Showed precise coordination between the surveillance system and transcription machinery in detecting faulty mRNA events.
- Observed that recruitment of quality control factors to defective mRNA genes occurs at the expense of their association with ncRNA genes, leading to ncRNA processing defects.
Conclusions:
- The mRNP quality control system is dynamically coordinated with transcription to ensure mRNA integrity.
- The recruitment of surveillance factors to aberrant mRNAs can disrupt the processing and termination of ncRNAs.
- This study provides insights into the intricate balance between mRNA quality control and ncRNA metabolism.
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