| 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 |
Related Documents
:
|
22107727 - Activation of mouse and human peroxisome proliferator-activated receptor-alpha (pparα)... 1919397 - Effect of the entero-pancreatic hormones, gastric inhibitory polypeptide and glucagon-l... 21625537 - Amyloid-associated nucleic acid hybridisation. 486517 - In vitro lipid metabolism in the rat pancreas. i. basal lipid metabolism. 19689417 - Snake venom l-amino acid oxidases: some consideration about their functional characteri... 1613507 - Changing fatty acid content of growth cone lipids prior to synaptogenesis. |
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: 2013-02-19 |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Case studies of the spatial heterogeneity of DNA viruses in the cystic fibrosis lung.
Next Document: Acute effects of salmeterol and fluticasone propionate alone and in combination on airway blood flow...