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Lookup NU author(s): Ricarda Richter, Dr Joanna Rorbach, Aleksandra Pajak, Dr Paul Smith, Professor Robert Lightowlers, Professor Zofia Chrzanowska-LightowlersORCiD
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. The EMBO Journal (2010) 29, 1116-1125. doi: 10.1038/emboj.2010.14; Published online 25 February 2010
Author(s): Richter R, Rorbach J, Pajak A, Smith PM, Wessels HJ, Huynen MA, Smeitink JA, Lightowlers RN, Chrzanowska-Lightowlers ZM
Publication type: Article
Publication status: Published
Journal: EMBO Journal
Year: 2010
Volume: 29
Issue: 6
Pages: 1116-1125
Print publication date: 01/03/2010
Date deposited: 22/04/2010
ISSN (print): 0261-4189
ISSN (electronic): 1460-2075
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/emboj.2010.14
DOI: 10.1038/emboj.2010.14
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