Zeitz, Michael J.Calhoun, Patrick J.James, Carissa C.Taetzsch, ThomasGeorge, Kijana K.Robel, StefanieValdez, GregorioSmyth, James W.2019-05-292019-05-292019-05-28http://hdl.handle.net/10919/89631Connexin43 (Cx43; gene name GJA1) is the most ubiquitously expressed gap junction protein, and understanding of its regulation largely falls under transcription and post-translational modification. In addition to Cx43, Gja1 mRNA encodes internally translated isoforms regulating gap junction formation, whose expression is modulated by TGF-b. Here, using RLM-RACE, we identify distinct Gja1 transcripts differing only in 50 UTR length, of which two are upregulated during TGF-b exposure and hypoxia. Introduction of these transcripts into Gja1/ cells phenocopies the response of Gja1 to TGF-b with reduced internal translation initiation. Inhibiting pathways downstream of TGF-b selectively regulates levels of Gja1 transcript isoforms and translation products. Reporter assays reveal enhanced translation of fulllength Cx43 from shorter Gja1 50 UTR isoforms. We also observe a correlation among UTR selection, translation, and reduced gap junction formation in aged heart tissue. These data elucidate a relationship between transcript isoform expression and translation initiation regulating intercellular communication.application/pdfen-USCreative Commons Attribution-NonCommercial-NoDerivs 4.0Article - Refereedhttps://doi.org/10.1016/j.celrep.2019.04.11427