| First Author | Zeitz MJ | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 9 | Pages | 2737-2747.e5 |
| PubMed ID | 31141695 | Mgi Jnum | J:301683 |
| Mgi Id | MGI:6489179 | Doi | 10.1016/j.celrep.2019.04.114 |
| Citation | Zeitz MJ, et al. (2019) Dynamic UTR Usage Regulates Alternative Translation to Modulate Gap Junction Formation during Stress and Aging. Cell Rep 27(9):2737-2747.e5 |
| abstractText | Connexin43 (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-beta. Here, using RLM-RACE, we identify distinct Gja1 transcripts differing only in 5' UTR length, of which two are upregulated during TGF-beta exposure and hypoxia. Introduction of these transcripts into Gja1-/- cells phenocopies the response of Gja1 to TGF-beta with reduced internal translation initiation. Inhibiting pathways downstream of TGF-beta selectively regulates levels of Gja1 transcript isoforms and translation products. Reporter assays reveal enhanced translation of full-length Cx43 from shorter Gja1 5' 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. |
