Internal translation of the connexin 43 transcript
Salat-Canela, Clàudia (Hospital Universitari Vall d'Hebron)
Sesé, Marta (Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain)
Peula, Cristina (Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain)
Ramón y Cajal, Santiago (Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain)
Aasen, Trond (Digestive Diseases Research Unit, Department of Gastroenterology, Institut de Recerca Vall d'Hebron, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain)
Universitat Autònoma de Barcelona

Data:	2014
Resum:	Connexin 43 (Cx43), the most widely expressed gap junction protein, is associated with a number of physiological and pathological conditions. Many functions of Cx43 have been shown to be independent of gap junction formation and only require the expression of Cx43 C-terminal fragments. Recent evidence demonstrated that naturally occurring C-terminal isoforms can be generated via internal translation. Here, we confirm that C-terminal domains of Cx43, particularly the major 20-kDa isoform, can be independently generated and regulated by internal translation of the same single GJA1 gene transcript that encodes full-length Cx43. Through direct RNA transfection experiments, we provide evidence that internal translation is not due to a bona fide cap-independent IRES-mediated mechanism, as upstream ribosomal scanning or translation is required. In addition to the mTOR pathway, we show for the first time, using both inhibitors and cells from knockout mice, that the Mnk1/2 pathway regulates the translation of the main 20-kDa isoform. Internal translation of the Cx43 transcript occurs but is not cap-independent and requires translation upstream of the internal start codon. In addition to the PI3K/AKT/mTOR pathway, the major 20-kDa isoform is regulated by the Mnk1/2 pathway. Our results have major implications for past and future studies escribing gap junction-independent functions of Cx43 in cancer and other pathological conditions. This study provides further clues to the signalling pathways that regulate internal mRNA translation, an emerging mechanism that allows for increased protein diversity and functional complexity from a single mRNA transcript.
Ajuts:	Instituto de Salud Carlos III PI13-00763
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Gap junction ; Connexin 43 ; IRES ; Mnk ; Mtor ; Cap-dependent ; Internal translation
Publicat a:	Cell communication and signaling, Vol. 12 (may 2014) , p. 31, ISSN 1478-811X

DOI: 10.1186/1478-811X-12-31
PMID: 24884945

6 p, 646.3 KB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats