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Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM).
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
2009 (English)In: PLoS genetics, ISSN 1553-7404, Vol. 5, no 7, e1000561- p.Article in journal (Refereed) Published
Abstract [en]

Elongator is a six subunit protein complex, conserved from yeast to humans. Mutations in the human Elongator homologue, hELP1, are associated with the neurological disease familial dysautonomia. However, how Elongator functions in metazoans, and how the human mutations affect neural functions is incompletely understood. Here we show that in Caenorhabditis elegans, ELPC-1 and ELPC-3, components of the Elongator complex, are required for the formation of the 5-carbamoylmethyl and 5-methylcarboxymethyl side chains of wobble uridines in tRNA. The lack of these modifications leads to defects in translation in C. elegans. ELPC-1::GFP and ELPC-3::GFP reporters are strongly expressed in a subset of chemosensory neurons required for salt chemotaxis learning. elpc-1 or elpc-3 gene inactivation causes a defect in this process, associated with a posttranscriptional reduction of neuropeptide and a decreased accumulation of acetylcholine in the synaptic cleft. elpc-1 and elpc-3 mutations are synthetic lethal together with those in tuc-1, which is required for thiolation of tRNAs having the 5'methylcarboxymethyl side chain. elpc-1; tuc-1 and elpc-3; tuc-1 double mutants display developmental defects. Our results suggest that, by its effect on tRNA modification, Elongator promotes both neural function and development.

Place, publisher, year, edition, pages
2009. Vol. 5, no 7, e1000561- p.
Identifiers
URN: urn:nbn:se:umu:diva-32160DOI: 10.1371/journal.pgen.1000561PubMedID: 19593383OAI: oai:DiVA.org:umu-32160DiVA: diva2:301381
Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2011-04-28Bibliographically approved
In thesis
1. The role of Elongator complex in Saccharomyces cerevisiae and Caenorhabditis elegans
Open this publication in new window or tab >>The role of Elongator complex in Saccharomyces cerevisiae and Caenorhabditis elegans
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Umeå: Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), Umeå Universitet, 2011. 38 p.
Identifiers
urn:nbn:se:umu:diva-43348 (URN)978-91-7459-176-7 (ISBN)
Public defence
2011-05-20, Byggnad 6 L, Major Groove, Umeå universitet, Umeå, 10:00 (English)
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Supervisors
Available from: 2011-04-29 Created: 2011-04-27 Last updated: 2011-04-28Bibliographically approved

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Chen, ChangchunTuck, SimonByström, Anders S

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Department of Molecular Biology (Faculty of Science and Technology)Umeå Centre for Molecular Medicine (UCMM)Department of Molecular Biology (Faculty of Medicine)

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