Pat1 Couples mRNA Decay with Ribosome-associated Quality Control
Abstract
Ribosome collisions induced by defective mRNAs trigger mRNA degradation and the ribosome-associated quality control (RQC) pathway, which eliminates the associated nascent peptide. Upon ribosome stalling, collided ribosomes are remodeled by the Ribosome Quality Triggering (RQT) complex, allowing the nascent peptide remaining attached to the released 60S ribosomal subunit to be recognized by the RQC machinery and targeted for degradation.
In parallel, defective mRNAs undergo decapping followed by 5′-3′ degradation by the exoribonuclease Xrn1. How these pathways are coordinated remains largely unknown. Here, we identify the conserved decapping activator Pat1 as a key regulator linking mRNA decay to ribosome-associated quality control. We show that Pat1 remains associated with decaycommitted stalled mRNPs before ribosome dissociation. Separation-of-function PAT1 mutants uncouple mRNA stabilization from nascent peptide degradation, and efficient nascent peptide degradation in one PAT1 mutant correlates with enhanced association of the RQT helicase Slh1 and reduced ribosome occupancy at the stalling site. Together, our study identifies Pat1 as the molecular link that coordinates decay-committed mRNPs with RQT-mediated ribosome remodeling and efficient RQC-dependent degradation of nascent peptides.
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BibTeX
@misc{ferrand2026pat1,
title = {{Pat1 Couples mRNA Decay with Ribosome-associated Quality Control}},
author = {Gabin Ferrand and Théa Bouez and Claire Torchet and Lionel Benard},
howpublished = {HAL},
year = {2026},
month = aug,
doi = {10.21203/rs.3.rs-10510622/v1},
url = {https://hal.science/hal-05781947v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Pat1 Couples mRNA Decay with Ribosome-associated Quality Control
AU - Gabin Ferrand
AU - Théa Bouez
AU - Claire Torchet
AU - Lionel Benard
PY - 2026
DA - 2026/08/13
PB - HAL
DO - 10.21203/rs.3.rs-10510622/v1
UR - https://hal.science/hal-05781947v1
AB - Ribosome collisions induced by defective mRNAs trigger mRNA degradation and the ribosome-associated quality control (RQC) pathway, which eliminates the associated nascent peptide. Upon ribosome stalling, collided ribosomes are remodeled by the Ribosome Quality Triggering (RQT) complex, allowing the nascent peptide remaining attached to the released 60S ribosomal subunit to be recognized by the RQC machinery and targeted for degradation. In parallel, defective mRNAs undergo decapping followed by 5′-3′ degradation by the exoribonuclease Xrn1. How these pathways are coordinated remains largely unknown. Here, we identify the conserved decapping activator Pat1 as a key regulator linking mRNA decay to ribosome-associated quality control. We show that Pat1 remains associated with decaycommitted stalled mRNPs before ribosome dissociation. Separation-of-function PAT1 mutants uncouple mRNA stabilization from nascent peptide degradation, and efficient nascent peptide degradation in one PAT1 mutant correlates with enhanced association of the RQT helicase Slh1 and reduced ribosome occupancy at the stalling site. Together, our study identifies Pat1 as the molecular link that coordinates decay-committed mRNPs with RQT-mediated ribosome remodeling and efficient RQC-dependent degradation of nascent peptides.
ER -