دورية أكاديمية
أعرض في EDS

The polypyrimidine tract binding protein regulates desaturase alternative splicing and PUFA composition.

التفاصيل البيبلوغرافية
العنوان: The polypyrimidine tract binding protein regulates desaturase alternative splicing and PUFA composition.
المؤلفون: Reardon HT; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853., Park WJ; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853., Zhang J; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853., Lawrence P; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853., Kothapalli KSD; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853., Brenna JT; Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853. Electronic address: jtb4@cornell.edu.
المصدر: Journal of lipid research [J Lipid Res] 2011 Dec; Vol. 52 (12), pp. 2279-2286. Date of Electronic Publication: 2011 Oct 06.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0376606 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1539-7262 (Electronic) Linking ISSN: 00222275 NLM ISO Abbreviation: J Lipid Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2021- : [New York] : Elsevier
Original Publication: Memphis, Lipid Research, inc.
مواضيع طبية MeSH: Alternative Splicing/*genetics , Fatty Acid Desaturases/*genetics , Fatty Acids, Omega-3/*metabolism , Fatty Acids, Omega-6/*metabolism , Heterogeneous-Nuclear Ribonucleoproteins/*metabolism , Polypyrimidine Tract-Binding Protein/*metabolism, Animals ; Exons/genetics ; Fatty Acid Desaturases/deficiency ; Gene Knockdown Techniques ; Gene Silencing ; Hep G2 Cells ; Heterogeneous-Nuclear Ribonucleoproteins/deficiency ; Heterogeneous-Nuclear Ribonucleoproteins/genetics ; Humans ; Papio ; Polypyrimidine Tract-Binding Protein/deficiency ; Polypyrimidine Tract-Binding Protein/genetics ; Protein Binding ; RNA Splice Sites/genetics ; RNA, Small Interfering/genetics ; Up-Regulation
مستخلص: The Δ6 desaturase, encoded by FADS2, plays a crucial role in omega-3 and omega-6 fatty acid synthesis. These fatty acids are essential components of the central nervous system, and they act as precursors for eicosanoid signaling molecules and as direct modulators of gene expression. The polypyrimidine tract binding protein (PTB or hnRNP I) is a splicing factor that regulates alternative pre-mRNA splicing. Here, PTB is shown to bind an exonic splicing silencer element and repress alternative splicing of FADS2 into FADS2 AT1. PTB and FADS2AT1 were inversely correlated in neonatal baboon tissues, implicating PTB as a major regulator of tissue-specific FADS2 splicing. In HepG2 cells, PTB knockdown modulated alternative splicing of FADS2, as well as FADS3, a putative desaturase of unknown function. Omega-3 fatty acids decreased by nearly one half relative to omega-6 fatty acids in PTB knockdown cells compared with controls, with a particularly strong decrease in eicosapentaenoic acid (EPA) concentration and its ratio to arachidonic acid (ARA). This is a rare demonstration of a mechanism specifically altering the cellular omega-3 to omega-6 fatty acid ratio without any change in diet/media. These findings reveal a novel role for PTB, regulating availability of membrane components and eicosanoid precursors for cell signaling.
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معلومات مُعتمدة: T32 HD052471 United States HD NICHD NIH HHS; T32HD052471 United States HD NICHD NIH HHS
المشرفين على المادة: 0 (Fatty Acids, Omega-3)
0 (Fatty Acids, Omega-6)
0 (Heterogeneous-Nuclear Ribonucleoproteins)
0 (PTBP1 protein, human)
0 (RNA Splice Sites)
0 (RNA, Small Interfering)
139076-35-0 (Polypyrimidine Tract-Binding Protein)
EC 1.14.19.- (Fatty Acid Desaturases)
EC 1.14.19.3 (FADS2 protein, human)
EC 1.14.19.3 (FADS3 protein, human)
تواريخ الأحداث: Date Created: 20111008 Date Completed: 20120319 Latest Revision: 20211020
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3220295
DOI: 10.1194/jlr.M019653
PMID: 21980057
قاعدة البيانات: MEDLINE
الوصف
تدمد:1539-7262
DOI:10.1194/jlr.M019653