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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220295PMC
http://dx.doi.org/10.1194/jlr.M019653DOI Listing

Publication Analysis

Top Keywords

alternative splicing
12
omega-6 fatty
12
fatty acids
12
polypyrimidine tract
8
tract binding
8
binding protein
8
omega-3 omega-6
8
fatty acid
8
splicing fads2
8
ptb knockdown
8

Similar Publications

The effect of LARP7 on gene expression during osteogenesis.

Mol Biol Rep

January 2025

Institute of Health Sciences, Department of Medical and Surgical Research, Hacettepe University, Ankara, Turkey.

Background: La-related protein 7 (LARP7) is a key regulator of RNA metabolism and is thought to play a role in various cellular processes. LARP7 gene autosomal recessive mutations are the cause of Alazami syndrome, which presents with skeletal abnormalities, intellectual disabilities, and facial dysmorphisms. This study aimed to determine the role of LARP7 in modulating gene expression dynamics during osteogenesis.

View Article and Find Full Text PDF

The chromosome 5p15.33 region, which encodes telomerase reverse transcriptase (TERT), harbors multiple germline variants identified by genome-wide association studies (GWAS) as risk for some cancers but protective for others. We characterized a variable number tandem repeat within intron 6 (VNTR6-1, 38-bp repeat unit) and observed a strong association between VNTR6-1 alleles (Short: 24-27 repeats, Long: 40.

View Article and Find Full Text PDF

Identification of pennaceous barbule cell factor (PBCF), a novel gene with spatiotemporal expression in barbule cells during feather development.

Gene

January 2025

Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Kitaku, Tsushimanaka, Okayama 700-8530, Japan; Graduate School of Environmental, Life, Natural Science and Technology, Okayama University, 3-1-1 Kitaku, Tsushimanaka, Okayama 700-8530, Japan. Electronic address:

Bird contour feathers exhibit a complex hierarchical structure composed of a rachis, barbs, and barbules, with barbules playing a crucial role in maintaining feather structure and function. Understanding the molecular mechanisms underlying barbule formation is essential for advancing our knowledge of avian biology and evolution. In this study, we identified a novel gene, pennaceous barbule cell factor (PBCF), using microarray analysis, RT-PCR, and in situ hybridization.

View Article and Find Full Text PDF

5-Methylcytosine-modified circRNA-CCNL2 regulates vascular remdeling in hypoxic pulmonary hypertension through binding to FXR2.

Int J Biol Macromol

January 2025

Central Laboratory of Harbin Medical University (Daqing), Daqing 163319, PR China; College of Pharmacy, Harbin Medical University, Harbin 150081, PR China; Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, Harbin Medical University, Harbin 150081, PR China. Electronic address:

Pulmonary hypertension (PH) is a malignant cardiovascular disease with a complex etiology. 5-Methylcytosine (m5C) is a post-transcriptional RNA modification identified in both stable and highly abundant RNAs, with a lower frequency of occurrence in circular RNAs (circRNAs). Nevertheless, the function of m5C-modified circRNAs in the pathogenesis of PH remains uncertain.

View Article and Find Full Text PDF

CLIPA protein pairs function as cofactors for prophenoloxidase activation in Anopheles gambiae.

Insect Biochem Mol Biol

January 2025

Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, OK 74078, USA. Electronic address:

Insect prophenoloxidases (proPO) are activated during immune responses by a proPO activating protease (PAP) in the presence of a high molecular weight cofactor assembled from serine protease homologs (SPH) that lack proteolytic activity. PAPs and the SPHs have a similar architecture, with an amino-terminal clip domain and a carboxyl-terminal protease domain. The SPHs belong to CLIPA subfamily of SP-related proteins.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!