{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T13:23:53Z","timestamp":1754486633022,"version":"3.37.3"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Eric Alterman Foundation for FD Cure"},{"DOI":"10.13039\/100008221","name":"Cure Starts Now Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008221","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent research on familial dysautonomia (FD) has focused on the development of therapeutics that facilitate the production of the correctly spliced, exon 20-containing, transcript in cells and individuals bearing the splice-altering, FD-causing mutation in the elongator acetyltransferase complex subunit I (ELP1) gene. We report here the ability of carnosol, a diterpene present in plant species of the Lamiaceae family, including rosemary, to enhance the cellular presence of the correctly spliced ELP1 transcript in FD patient-derived fibroblasts by upregulating transcription of the ELP1 gene and correcting the aberrant splicing of the ELP1 transcript. Carnosol treatment also elevates the level of the RNA binding motif protein 24 (RBM24) and RNA binding motif protein 38 (RBM38) proteins, two multifunctional RNA-binding proteins. Transfection-mediated expression of either of these RNA binding motif (RBMs) facilitates the inclusion of exon 20 sequence into the transcript generated from a minigene-bearing ELP1 genomic sequence containing the FD-causing mutation. Suppression of the carnosol-mediated induction of either of these RBMs, using targeting siRNAs, limited the carnosol-mediated inclusion of the ELP1 exon 20 sequence. Carnosol treatment of FD patient peripheral blood mononuclear cells facilitates the inclusion of exon 20 into the ELP1 transcript. The increased levels of the ELP1 and RBM38 transcripts and the alternative splicing of the sirtuin 2 (SIRT2) transcript, a sentinel for exon 20 inclusion in the FD-derived ELP1 transcript, are observed in RNA isolated from whole blood of healthy adults following the ingestion of carnosol-containing rosemary extract. These findings and the excellent safety profile of rosemary together justify an expedited clinical study of the impact of carnosol on the FD patient population.<\/jats:p>","DOI":"10.1093\/hmg\/ddac133","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T14:05:13Z","timestamp":1655388313000},"page":"3521-3538","source":"Crossref","is-referenced-by-count":2,"title":["Carnosol, a diterpene present in rosemary, increases ELP1 levels in familial dysautonomia patient-derived cells and healthy adults: a possible therapy for FD"],"prefix":"10.1093","volume":"31","author":[{"given":"Sylvia L","family":"Anderson","sequence":"first","affiliation":[{"name":"Laboratory for Familial Dysautonomia Research , Department of Biological Sciences, Fordham University, Bronx, NY 10458 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faaria","family":"Fasih-Ahmad","sequence":"additional","affiliation":[{"name":"Laboratory for Familial Dysautonomia Research , Department of Biological Sciences, Fordham University, Bronx, NY 10458 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J","family":"Evans","sequence":"additional","affiliation":[{"name":"Laboratory for Familial Dysautonomia Research , Department of Biological Sciences, Fordham University, Bronx, NY 10458 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8254-5634","authenticated-orcid":false,"given":"Berish Y","family":"Rubin","sequence":"additional","affiliation":[{"name":"Laboratory for Familial Dysautonomia Research , Department of Biological Sciences, Fordham University, Bronx, NY 10458 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"2022101308084935200_ref1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.2147\/TACG.S129638","article-title":"IKBKAP\/ELP1 gene mutations: mechanisms of familial dysautonomia and gene-targeting therapies","volume":"10","author":"Rubin","year":"2017","journal-title":"Appl. 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Food Res."},{"key":"2022101308084935200_ref10","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1111\/febs.12355","article-title":"Cardiac glycosides correct aberrant splicing of IKBKAP-encoded mRNA in familial dysautonomia derived cells by suppressing expression of SRSF3","volume":"280","author":"Liu","year":"2013","journal-title":"FEBS J."},{"key":"2022101308084935200_ref11","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1073\/pnas.1415525112","article-title":"Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia","volume":"112","author":"Yoshida","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2022101308084935200_ref12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.bbrc.2005.08.054","article-title":"Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia","volume":"336","author":"Anderson","year":"2005","journal-title":"Biochem. Biophys. Res. 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Genet."},{"key":"2022101308084935200_ref31","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3390\/cells10040923","article-title":"Regulation of RNA splicing: aberrant splicing regulation and therapeutic targets in cancer","volume":"10","author":"Kitamura","year":"2021","journal-title":"Cell"},{"key":"2022101308084935200_ref32","doi-asserted-by":"crossref","first-page":"100728","DOI":"10.1016\/j.drup.2020.100728","article-title":"The role of alternative splicing in cancer: from oncogenesis to drug resistance","volume":"53","author":"Sciarrillo","year":"2020","journal-title":"Drug Resist. Updat."},{"key":"2022101308084935200_ref33","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3727\/096368912X655154","article-title":"Aberrant alternative splicing events in Parkinson's disease","volume":"22","author":"Fu","year":"2013","journal-title":"Cell Transplant."},{"key":"2022101308084935200_ref34","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.3390\/genes12081272","article-title":"Alternative splicing and hypoxia puzzle in Alzheimer's and Parkinson's diseases","volume":"12","author":"Jakubauskien\u0117","year":"2021","journal-title":"Genes (Basel)"},{"key":"2022101308084935200_ref35","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s40520-019-01360-x","article-title":"Alternative splicing in Alzheimer's disease","volume":"33","author":"Biamonti","year":"2021","journal-title":"Aging Clin. Exp. Res."},{"key":"2022101308084935200_ref36","doi-asserted-by":"crossref","first-page":"713540","DOI":"10.3389\/fimmu.2021.713540","article-title":"Alternative splicing: a new cause and potential therapeutic target in autoimmune disease","volume":"12","author":"Ren","year":"2021","journal-title":"Front. Immunol."},{"key":"2022101308084935200_ref37","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1101\/gad.2014311","article-title":"Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin a","volume":"25","author":"Corrionero","year":"2011","journal-title":"Genes Dev."},{"key":"2022101308084935200_ref38","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/nar\/gkz1132","article-title":"Hybridization-mediated off-target effects of splice-switching antisense oligonucleotides","volume":"48","author":"Scharner","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2022101308084935200_ref39","doi-asserted-by":"crossref","first-page":"8378","DOI":"10.3390\/ijms22168378","article-title":"High concentration of an ISS-N1-targeting antisense oligonucleotide causes massive perturbation of the transcriptome","volume":"22","author":"Ottesen","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2022101308084935200_ref40","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/gtc.12587","article-title":"Estimated number of off-target candidate sites for antisense oligonucleotides in human mRNA sequences","volume":"23","year":"2018","journal-title":"Genes Cells."},{"key":"2022101308084935200_ref41","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/ALN.0b013e318267084d","article-title":"Case scenario: perioperative administration of tocotrienols and green tea extract in a child with familial dysautonomia","volume":"117","author":"Cook-Sather","year":"2012","journal-title":"Anesthesiology"},{"key":"2022101308084935200_ref42","first-page":"1","article-title":"Use of rosemary extracts as a food additive: scientific opinion of the panel on food additives, flavourings, processing aids and materials in contact with food","volume":"721","author":"Aguilar","year":"2008","journal-title":"EFSA J."},{"key":"2022101308084935200_ref43","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the regulation of protein abundance from proteomic and transcriptomic analyses","volume":"13","author":"Vogel","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"2022101308084935200_ref44","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"2022101308084935200_ref45","first-page":"1053","volume-title":"Principles and Practice of Genitourinary Oncology","author":"Biedler","year":"1997"},{"key":"2022101308084935200_ref46","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1038\/sj.onc.1202621","article-title":"HuD, a neuronal-specific RNA-binding protein, is a putative regulator of N-myc pre-mRNA processing\/stability in malignant human neuroblasts","volume":"18","author":"Lazarova","year":"1999","journal-title":"Oncogene"},{"key":"2022101308084935200_ref47"},{"key":"2022101308084935200_ref48","first-page":"2522","article-title":"Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein\/p300-dependent and -independent mechanisms","volume":"62","author":"Subbaramaiah","year":"2002","journal-title":"Cancer Res."},{"key":"2022101308084935200_ref49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2011.02.005","article-title":"Carnosol: a promising anti-cancer and anti-inflammatory agent","volume":"305","author":"Johnson","year":"2011","journal-title":"Cancer Lett."},{"key":"2022101308084935200_ref50","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1097\/01.wnr.0000239951.14954.10","article-title":"Carnosol, a component of rosemary (Rosmarinus officinalis L.) protects nigral dopaminergic neuronal cells","volume":"17","author":"Kim","year":"2006","journal-title":"Neuroreport"},{"key":"2022101308084935200_ref51","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1007\/s12035-015-9519-1","article-title":"The dietary components carnosic acid and carnosol as neuroprotective agents: a mechanistic view","volume":"53","author":"Oliveira","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"2022101308084935200_ref52","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1039\/c4fo00023d","article-title":"Antitumor activity of the dietary diterpene carnosol against a panel of human cancer cell lines","volume":"5","author":"Vergara","year":"2014","journal-title":"Food Funct."},{"key":"2022101308084935200_ref53","doi-asserted-by":"crossref","first-page":"e109630","DOI":"10.1371\/journal.pone.0109630","article-title":"Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer","volume":"9","author":"Al Dhaheri","year":"2014","journal-title":"PLoS One"},{"key":"2022101308084935200_ref54","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.biocel.2016.02.019","article-title":"New insights into the anticancer activity of carnosol: p53 reactivation in the U87MG human glioblastoma cell line","volume":"74","author":"Giacomelli","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2022101308084935200_ref55","doi-asserted-by":"crossref","first-page":"743","DOI":"10.3389\/fonc.2019.00743","article-title":"Carnosol, a natural polyphenol, inhibits migration, metastasis, and tumor growth of breast cancer via a ROS-dependent proteasome degradation of STAT3","volume":"9","author":"Alsamri","year":"2019","journal-title":"Front. Oncol."},{"key":"2022101308084935200_ref56","doi-asserted-by":"crossref","first-page":"961","DOI":"10.3390\/antiox9100961","article-title":"Anticancer properties of carnosol: a summary of in vitro and in vivo evidence","volume":"9","author":"O'Neill","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"2022101308084935200_ref57","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3390\/ph11020033","article-title":"Phytochemical study of the Ecuadorian species Lepechinia mutica (Benth.) Epling and high antifungal activity of carnosol against Pyricularia oryzae","volume":"11","author":"Ram\u00edrez","year":"2018","journal-title":"Pharmaceuticals (Basel)"},{"key":"2022101308084935200_ref58","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1142\/S0192415X20500664","article-title":"Antidiabetic effects and mechanisms of rosemary (Rosmarinus officinalis L.) and its phenolic components","volume":"48","author":"Bao","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"2022101308084935200_ref59","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0278-6915(96)00004-X","article-title":"An evaluation of the antioxidant and antiviral action of extracts of rosemary and Proven\u00e7al herbs","volume":"34","author":"Aruoma","year":"1996","journal-title":"Food Chem. Toxicol."},{"key":"2022101308084935200_ref60","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/1743-422X-10-303","article-title":"Antiviral activity of carnosic acid against respiratory syncytial virus","volume":"10","author":"Shin","year":"2013","journal-title":"Virol. J."},{"key":"2022101308084935200_ref61","doi-asserted-by":"crossref","first-page":"106978","DOI":"10.1016\/j.intimp.2020.106978","article-title":"Carnosol attenuates RANKL-induced osteoclastogenesis in vitro and LPS-induced bone loss","volume":"89","author":"Chen","journal-title":"Int. Immunopharmacol."},{"key":"2022101308084935200_ref62","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/jcp.29978","article-title":"Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis","volume":"236","author":"Li","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"2022101308084935200_ref63","doi-asserted-by":"crossref","first-page":"197","DOI":"10.4196\/kjpp.2021.25.3.197","article-title":"Carnosol induces the osteogenic differentiation of bone marrow-derived mesenchymal stem cells via activating BMP-signaling pathway","volume":"25","author":"Abdallah","year":"2021","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"2022101308084935200_ref64","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.foodchem.2012.09.028","article-title":"Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L","volume":"136","author":"Machado","year":"2013","journal-title":"Food Chem."},{"key":"2022101308084935200_ref65","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1002\/mnfr.201300052","article-title":"Bioavailability of the major bioactive diterpenoids in a rosemary extract: metabolic profile in the intestine, liver, plasma, and brain of Zucker rats","volume":"57","author":"Romo Vaquero","year":"2013","journal-title":"Mol. Nutr. 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Pharmacol."},{"key":"2022101308084935200_ref69","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1089\/jmf.2011.0005","article-title":"Short-term study on the effects of rosemary on cognitive function in an elderly population","volume":"15","author":"Pengelly","year":"2012","journal-title":"J. Med. Food"},{"key":"2022101308084935200_ref70","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ctcp.2017.11.004","article-title":"Effects of Rosmarinus officinalis L. on memory performance, anxiety, depression, and sleep quality in university students: a randomized clinical trial","volume":"30","author":"Nematolahi","year":"2018","journal-title":"Complement. Ther. Clin. 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