iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation

Year: 2021

Type: article

Abstract: Post-translational modification of ribosomal proteins enables rapid and dynamic regulation of protein biogenesis. Site-specific ubiquitylation of 40S ribosomal proteins uS10 and eS10 plays a key role during ribosome-associated quality control (RQC). Distinct, and previously functionally ambiguous, ubiquitylation events on the 40S proteins uS3 and uS5 are induced by diverse proteostasis stressors that impact translation activity. Here, we identify the ubiquitin ligase RNF10 and the deubiquitylating enzyme USP10 as the key enzymes that regulate uS3 and uS5 ubiquitylation. Prolonged uS3 and uS5 ubiquitylation results in 40S, but not 60S, ribosomal protein degradation in a manner independent of canonical autophagy. We show that blocking progression of either scanning or elongating ribosomes past the start codon triggers site-specific ubiquitylation events on ribosomal proteins uS5 and uS3. This study identifies and characterizes a distinct arm in the RQC pathway, initiation RQC (iRQC), that acts on 40S ribosomes during translation initiation to modulate translation activity and capacity.

Source: Cell Reports

DOI: 10.1016/j.celrep.2021.109642

Authors: Danielle M. Garshott, Heeseon An, Elayanambi Sundaramoorthy, Marilyn Leonard, Alison Vicary, J. Wade Harper, Eric J. Bennett

Institutions: University of California San Diego, Harvard University

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $5,200

Funders: National Science Foundation, Harvard Medical School, National Institutes of Health, University of California, San Diego, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke

OpenAlex ID: W3196366141