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Alternative splicing of fatty acid desaturases is associated with altered fatty acid composition
Author(s) -
Reardon Holly T.,
Kothapalli Kumar S. D.,
Park Woo Jung,
Zhang Jimmy,
Lawrence Peter,
Brenna J. Thomas
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.105.7
Subject(s) - fads2 , fatty acid desaturase , rna splicing , alternative splicing , eicosapentaenoic acid , biology , fatty acid , biochemistry , polyunsaturated fatty acid , microbiology and biotechnology , docosahexaenoic acid , gene , messenger rna , rna
The delta‐6 desaturase, encoded by FADS2 , plays a crucial role in omega‐3 and omega‐6 fatty acid synthesis. We have recently identified an alternative transcript of FADS2 ( FADS2 AT1 ) and 7 alternative transcripts for the putative desaturase FADS3. Here, we investigated regulation of desaturase alternative splicing, and fatty acid changes associated with altered splicing patterns. We hypothesized a role for the splicing repressor PTB/hnRNP I based on bioinformatics predictions of splicing factor binding sites. PTB and FADS2AT1 were inversely correlated in infant baboon tissues, implicating PTB as a major regulator of tissue‐specific FADS2 splicing. In human liver‐derived HepG2 cells, siRNA knockdown of PTB led to upregulation of FADS2 AT1 and FADS3 AT7 . This splicing pattern was associated with a specific decrease in the ratio of total cellular omega‐3 to omega‐6 fatty acids, including a nearly 2‐fold decrease in eicosapentaenoic acid (EPA) content, and a 43% reduction in the ratio of EPA with arachidonic acid (ARA). These findings reveal a novel mechanism controlling availability of eicosanoid precursors for cell signaling. H. R. was supported by a Ruth L. Kirchstein‐NRSA predoctoral fellowship in reproductive sciences and genomics (Grant Number T32HD052471) from the National Institutes of Child Health and Human Development.