A Functional Peptidyl-tRNA Hydrolase, ICT1, Has Been Recruited into the Human Mitochondrial Ribosome

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2010 Feb 27

PMID 20186120

Citations 91

Authors

Ricarda Richter

Joanna Rorbach

Aleksandra Pajak

Paul M Smith

Hans J Wessels

Martijn A Huynen

Jan A Smeitink

Robert N Lightowlers

Zofia M Chrzanowska-Lightowlers

Affiliations

Soon will be listed here.

Abstract

Bioinformatic analysis classifies the human protein encoded by immature colon carcinoma transcript-1 (ICT1) as one of a family of four putative mitochondrial translation release factors. However, this has not been supported by any experimental evidence. As only a single member of this family, mtRF1a, is required to terminate the synthesis of all 13 mitochondrially encoded polypeptides, the true physiological function of ICT1 was unclear. Here, we report that ICT1 is an essential mitochondrial protein, but unlike the other family members that are matrix-soluble, ICT1 has become an integral component of the human mitoribosome. Release-factor assays show that although ICT1 has retained its ribosome-dependent PTH activity, this is codon-independent; consistent with its loss of both domains that promote codon recognition in class-I release factors. Mutation of the GGQ domain common to ribosome-dependent PTHs causes a loss of activity in vitro and, crucially, a loss of cell viability, in vivo. We suggest that ICT1 may be essential for hydrolysis of prematurely terminated peptidyl-tRNA moieties in stalled mitoribosomes.

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