Background Connexins (Cxs) are integral membrane proteins that form plasma membrane channels, allowing cell-matrix and cell to cell communication. Initially described in joining excitable cells (nerve and muscle), gap junctions (GJs) are found joining virtually all cells in solid tissues and are essential for the functional co-ordination of organs by enabling direct transfer of small signalling molecules, metabolites, ions, and electrical signals. Several studies have revealed diverse channel-independent functions of Cxs, including control of cell growth and tumorigenicity. Chondrocytes from osteoarthritic cartilage have increased expression of connexin 43 (Cx43). The myriad roles of Cx43 and its implication in the development of diseases such as cancer, osteoarthritis or alzheimer have rise to many novel questions.
Objectives The aim of this study was to investigate possible RNA binding domains in the Cx43 and Cx26 sequences in order to study if cells are able to exchange molecules of RNA anchored to Cx43/Cx26 sequences present in exosomes or vesicles.
Methods Amino acids sequences from Cx43 and Connexin 26 (Cx26) were obtained from the Protein Database (NCBI) and the Cx26 structure from the Protein Data Bank (RCSB) . Protein sequences from both Cxs were aligned and compared with Protein Blast and Lalign servers. Analysis of RNA-binding propensity of Cx43 and Cx26 sequences was evaluated with three computational methods with the high predicting accuracy  aaRNA, Bind+ and Pprint.
Results Protein sequences were highly conserved between Cx43 and Cx26 with the exception of the the C-terminal end (CTD). The combination of the scores obtained from the three predictors showed four domains that potentially interact with RNA sequences. Two of these domains include the intracellular loop (ICL) and the CTD.
Conclusions Our results suggest that Cx43 and Cx26 are able to interact with RNA targets including siRNA and mRNA. These interactions would have a range of potential implications for cellular communication and control of signalling pathways.
Maeda S et al. Nature 458: 597–602.
Nagarajan R et al. PLos ONE 9 (3): e91140.
Disclosure of Interest None declared
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