Document Detail


The polypyrimidine tract binding protein regulates desaturase alternative splicing and PUFA composition.
MedLine Citation:
PMID:  21980057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Holly T Reardon; Woo Jung Park; Jimmy Zhang; Peter Lawrence; Kumar S D Kothapalli; J Thomas Brenna
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-06
Journal Detail:
Title:  Journal of lipid research     Volume:  52     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-03-19     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2279-86     Citation Subset:  IM    
Affiliation:
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
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MeSH Terms
Descriptor/Qualifier:
Alternative Splicing / genetics*
Animals
Exons / genetics
Fatty Acid Desaturases / deficiency,  genetics*
Fatty Acids, Omega-3 / metabolism*
Fatty Acids, Omega-6 / metabolism*
Gene Knockdown Techniques
Gene Silencing
Hep G2 Cells
Heterogeneous-Nuclear Ribonucleoproteins / deficiency,  genetics,  metabolism*
Humans
Papio
Polypyrimidine Tract-Binding Protein / deficiency,  genetics,  metabolism*
Protein Binding
RNA Splice Sites / genetics
RNA, Small Interfering / genetics
Up-Regulation
Grant Support
ID/Acronym/Agency:
T32HD052471/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

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