Dynamic UTR Usage Regulates Alternative Translation to Modulate Gap Junction Formation during Stress and Aging
| dc.contributor.author | Zeitz, Michael J. | en |
| dc.contributor.author | Calhoun, Patrick J. | en |
| dc.contributor.author | James, Carissa C. | en |
| dc.contributor.author | Taetzsch, Thomas | en |
| dc.contributor.author | George, Kijana K. | en |
| dc.contributor.author | Robel, Stefanie | en |
| dc.contributor.author | Valdez, Gregorio | en |
| dc.contributor.author | Smyth, James W. | en |
| dc.date.accessioned | 2019-05-29T14:48:54Z | en |
| dc.date.available | 2019-05-29T14:48:54Z | en |
| dc.date.issued | 2019-05-28 | en |
| dc.description.abstract | 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-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. | en |
| dc.description.sponsorship | This work was supported by an NIH NHLBI R01 grant (HL132236 to J.W.S.), NHLBI F31 grant (HL140909 to C.C.J.), NIA R01 grant (AG055545 to G.V.), NINDS R21 grant (NS106313 to G.V.), NINDS R01 grant (NS105807 to S.R.), NINDS R21 grant (NS107941 to S.R.), and the American Heart Association (18PRE33960573 to P.J.C.). Funding for open access charge: NIH. | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1016/j.celrep.2019.04.114 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/89631 | en |
| dc.identifier.volume | 27 | en |
| dc.language.iso | en_US | en |
| dc.publisher | Elsevier | en |
| dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs 4.0 | en |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
| dc.title | Dynamic UTR Usage Regulates Alternative Translation to Modulate Gap Junction Formation during Stress and Aging | en |
| dc.title.serial | Cell Reports | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |