RQC2 is a major player in peptide release from stalled ribosomes

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Eukaryotic cells possess quality control mechanisms to prevent toxic polypeptide accumulation and ensure ribosome availability.
• The ribosome-associated quality control complex (RQC) is an evolutionarily conserved pathway involved in these processes.
• Previous research identified factors like ANKZF1/Vms1p, Ptrh1, and Arb1p in peptide-tRNA release from 60S ribosomal subunits.

Purpose of the Study:

• To identify genes involved in the release of peptides from stalled ribosomes.
• To investigate the molecular mechanism by which RQC2 influences peptide release.

Main Methods:

• Genetic screening to identify mutants affecting peptide release.
• Cryoelectron microscopy (cryo-EM) to determine the structure of the RQC complex with a specific mutation.
• Biochemical assays to assess the impact of the mutation on tRNA binding and CAT tailing.

Main Results:

• A mutant allele of RQC2 was identified as being involved in peptide release from stalled ribosomes.
• The cryo-EM structure revealed how the F340I mutation in RQC2 affects its binding within the RQC complex.
• This altered binding disrupts the A-site's ability to bind tRNA in the presence of Ltn1, limiting C-terminal alanine and threonine (CAT) tailing.

Conclusions:

• The Rqc2 protein plays a crucial role in peptide release from stalled ribosomes.
• The F340I mutation in RQC2 provides mechanistic insight into how RQC regulates peptide release and CAT tailing.
• These findings contribute to a model explaining the function of Rqc2 in ribosome-associated quality control.