Ribosome Quality Control (RQC) Project

Ribosome Quality Control (RQC) Project

Overview

Ribosome Quality Control (RQC) is a surveillance pathway that detects and resolves stalled or colliding ribosomes during translation. This prevents accumulation of aberrant proteins and maintains proteostasis. The field has seen major advances 2020+ with structural and mechanistic discoveries.

Model Species

Primary: Homo sapiens (human)
- Best characterized in human/mammalian systems
- Links to neurodegenerative disease (ALS, etc.)

Core Pathway Architecture

1. Collision Sensors

Detect ribosome collisions:
- ZNF598 - Ubiquitinates collided ribosomes (RPS10, RPS20)
- EDF1 - Collision sensor, recruits GIGYF2
- GIGYF2 - Recruits 4EHP to repress translation

2. Ribosome Splitting

Disassemble stalled ribosomes:
- PELO - Dom34 homolog, promotes subunit splitting
- HBS1L - GTPase, works with PELO
- ABCE1 - ATPase that physically separates subunits

3. RQC Complex

Handles 60S-nascent chain complexes:
- NEMF - Recruits LTN1, stabilizes nascent chain
- LTN1 - E3 ubiquitin ligase (Listerin)
- TCF25 - RQC complex component
- ANKZF1 - Vms1 homolog, releases stalled peptides

4. mRNA Decay

Targets problematic mRNAs:
- No-go decay pathway genes

5. Downstream Quality Control

Candidate Genes (~15)

Gene UniProt Function
ZNF598 Q86UK7 Collision sensor, E3 ligase
EDF1 O60869 Collision sensor
GIGYF2 Q6Y7W6 Translation repressor
PELO Q9BRX2 Ribosome rescue
HBS1L Q9Y450 GTPase for splitting
ABCE1 P61221 Ribosome splitting ATPase
NEMF O00762 RQC complex
LTN1 O94822 E3 ubiquitin ligase
TCF25 Q9BQ70 RQC complex
ANKZF1 Q9H8Y5 Peptide release
ASCC3 Q8N3C0 Helicase, collision resolution
ASCC2 Q9H1I8 ASCC complex
VCP P55072 AAA+ ATPase

Key Recent Discoveries (2020+)

Disease Relevance

Project Status