An AUG Codon Conserved for Protein Function Rather than Translational Initiation: The Story of the Protein sElk1

Article Article scientifique Article An AUG Codon Conserved for Protein Function Rather than Translational Initiation: The Story of the Protein sElk1 eng 2014 author Legrand Sobolewski Noémie 810559 author Araud Tanguy 629127 author Conne Béatrice 117948 author Kuijpers Odin Marcus Quirinus 678244 author Jaquier-Gubler Pascale 23175 author Curran Joseph 22465 e102890 10.1371/journal.pone.0102890 1932-6203 Elk1 belongs to the ternary complex (TCF) subfamily of the ETS-domain transcription factors. Several studies have implicated an important function for Elk1 in the CNS including synaptic plasticity and cell differentiation. Whilst studying ELK1 gene expression in rat brain a 54 aa N-terminally truncated isoform lacking the DBD was observed on immunoblots. A similar protein was also detected in NGF differentiated PC12 cells. It was proposed that this protein, referred to as sElk1, arose due to a de-novo initiation event at the second AUG codon on the Elk1 ORF. Transient over-expression of sElk1 potentiated neurite growth in the PC12 model and induced differentiation in the absence of NGF, leading to the proposition that it may have a specific function in the CNS. Here we report on the translational expression from the mouse and rat transcript and compare it with our earlier published work on human. Results demonstrate that the previously observed sElk1 protein is a non-specific band arising from the antibody employed. The tight conservation of the internal AUG reported to drive sElk1 expression is in fact coupled to Elk1 protein function, a result consistent with the Elk1-SRE crystal structure. It is also supported by the observed conservation of this methionine in the DBD of all ETS transcription factors independent of the N- or C-terminal positioning of this domain. Reporter assays demonstrate that elements both within the 5'UTR and downstream of the AUGElk1 serve to limit 40S access to the AUGsElk1 codon. Dewey 576.5 Dewey 590 Dewey 616 Swiss National Science Foundation The elk-1 gene: A model for how alternative splicing in the 5'UTR can modulate translational reinitiation in mammalian cells. 143772 CH Project funding 23 Institut de génétique et de génomique 0DH 54 Département de microbiologie et médecine moléculaire 21B 135 Département de médecine génétique et développement 21D false 365 Régulation traductionnelle dans les cellules de mammifère 631 PloS one 9 7 d35640e9-8d64-4e3a-89ab-28bd6cd83fea Article (Published version) Public LegrandPlos.pdf 4428361 application/pdf CC BY openAccess Centres et instituts / Institut de génétique et de génomique Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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An AUG Codon Conserved for Protein Function Rather than Translational Initiation: The Story of the Protein sElk1	PloS one			2014	716	243

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Kuijpers, Odin Marcus Quirinus