Recruitment of RNA molecules by connexin RNA-binding motifs: Implication in RNA and DNA transport through microvesicles and exosomes.
Connexins (Cxs) are integral membrane proteins that form high-conductance plasma membrane channels, allowing communication from cell to cell (via gap junctions) and from cells to the extracellular environment (via hemichannels). Initially described for their role in joining excitable cells (nerve and muscle), gap junctions (GJs) are found between virtually all cells in solid tissues and are essential for functional coordination by enabling the direct transfer of small signalling molecules, metabolites, ions, and electrical signals from cell to cell. Several studies have revealed diverse channel-independent functions of Cxs, which include the control of cell growth and tumourigenicity. Connexin43 (Cx43) is the most widespread Cx in the human body. The myriad roles of Cx43 and its implication in the development of disorders such as cancer, inflammation, osteoarthritis and Alzheimer's disease have given rise to many novel questions. Several RNA- and DNA-binding motifs were predicted in the Cx43 and Cx26 sequences using different computational methods. This review provides insights into new, ground-breaking functions of Cxs, highlighting important areas for future work such as transfer of genetic information through extracellular vesicles. We discuss the implication of potential RNA- and DNA-binding domains in the Cx43 and Cx26 sequences in the cellular communication and control of signalling pathways.
CellCOM research group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), Servizo Galego de Saúde (SERGAS), University of A Coruña, Xubias de Arriba, 84 15006 A Coruña, Spain.
Marta
M
Varela-Eirin
CellCOM research group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), Servizo Galego de Saúde (SERGAS), University of A Coruña, Xubias de Arriba, 84 15006 A Coruña, Spain.
Adrian
A
Varela-Vazquez
CellCOM research group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), Servizo Galego de Saúde (SERGAS), University of A Coruña, Xubias de Arriba, 84 15006 A Coruña, Spain.
Marina
M
Rodríguez-Candela Mateos
Grupo GIBE, Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade de A Coruña (UDC), Campus Zapateira, s/n 15.071, A Coruña, Spain.
Anton
A
Vila-Sanjurjo
CellCOM research group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), Servizo Galego de Saúde (SERGAS), University of A Coruña, Xubias de Arriba, 84 15006 A Coruña, Spain.
Eduardo
E
Fonseca
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Departamento de Química Inorgánica, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
José L
JL
Mascareñas
Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain; Departamento de Química Inorgánica, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
M
M
Eugenio Vázquez
CellCOM research group, Instituto de Investigación Biomédica de A Coruña (INIBIC), CH-Universitario A Coruña (XXIAC), Servizo Galego de Saúde (SERGAS), University of A Coruña, Xubias de Arriba, 84 15006 A Coruña, Spain. Electronic address: Ma.Dolores.Mayan.Santos@sergas.es.
Maria D
MD
Mayan
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001692:Biological Transport; D002450:Cell Communication; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D000072259:Connexin 26; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism*; D017629:Gap Junctions; D006801:Humans; D007249:Inflammation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054730:Protein Interaction Domains and Motifs; D012313:RNA / Q000235:genetics / Q000378:metabolism
D018031:Connexin 43; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D012313:RNA
Cellular communication; Connexin26; Connexin43; Exosomes; Microvesicles; RNA-binding domains