Fibronectin mRNA splice variant in articular cartilage lacks bases encoding the V, III-15, and I-10 protein segments.
Abstract: Fibronectin is an extracellular matrix glycoprotein encoded by a single gene. Alternative RNA splicing has been reported at three sites, ED (extra type III domain)-A, ED-B, and the variable or V region. Articular cartilage fibronectin monomers are rarely (ED-A)+, but approximately 25% are (ED-B)+. RNA gel electrophoresis and Northern blot analysis identified two (ED-B)+ and two (ED-B)- fibronectin transcripts in cartilage, each pair differing by approximately 750 bases. This difference results from a previously unreported RNA splicing pattern that eliminates not only the V region but also nucleotides encoding protein segments III-15 and I-10. This new splice variant, which we designate (V+C)-, represents the majority of fibronectin transcripts in equine, canine, and rabbit articular cartilage but is absent in the liver. Reverse transcriptase-polymerase chain reaction analyses of 11 additional equine tissues failed to detect the (V+C)- splice variant, except for very low levels in lymph node, bone, aorta, and skin. Furthermore, chondrocytes grown in monolayer culture maintain high levels of fibronectin expression but stop expressing (V+C)- transcripts over time. The tissue-specific expression pattern of this novel fibronectin isoform suggests that it may have an important function in the matrix organization of cartilage.
Publication Date: 1996-08-02 PubMed ID: 8702559DOI: 10.1074/jbc.271.31.18954Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research investigates a specific variant of fibronectin mRNA in articular cartilage, which lacks certain protein sections. The study suggests that this variant, unique to cartilage and not seen in other tissues such as the liver, might play a crucial role in the cartilage’s matrix organization.
What Fibronectin Is
- Fibronectin is a glycoprotein found in the extracellular matrix.
- It’s encoded by a single gene, which can produce distinct RNA splice variants, which affect the function and structure of fibronectin proteins.
Alternative RNA Splicing Sites and Current Findings
- The identified splice sites of this gene are known as ED-A, ED-B, and the V region.
- However, in articular cartilage, the fibronectin molecules seldom include the ED-A splice, but about 25% include the ED-B splice.
- RNA gel electrophoresis and Northern blot analysis have identified two each of ED-B positive and ED-B negative fibronectin transcripts.
- These pairs differ by around 750 bases due to a distinctive RNA splicing pattern that removes not only the V region but also the regions encoding protein segments III-15 and I-10.
The New Fibronectin Splice Variant
- This previously unseen splice variant has been named (V+C)-.
- It makes up the majority of fibronectin transcripts in equine, canine, and rabbit articular cartilage but is missing in the liver.
- Additional analysis with eleven other equine tissues failed to detect the (V+C)- splice variant, except in very low levels found in the lymph node, bone, aorta, and skin.
- Chondrocytes, when grown in monolayer culture, continue to express high levels of fibronectin but stop expressing the (V+C)- transcripts over time.
Potential Function of the Novel Fibronectin Variant
- The tissue-specific nature of the (V+C)- splice variant implies that it could play an important part in cartilage’s matrix organization.
- This could be a valuable area for further research, as understanding the role of this variant may lead to better understanding and potential treatments for diseases affecting the cartilage such as osteoarthritis.
Cite This Article
APA
MacLeod JN, Burton-Wurster N, Gu DN, Lust G.
(1996).
Fibronectin mRNA splice variant in articular cartilage lacks bases encoding the V, III-15, and I-10 protein segments.
J Biol Chem, 271(31), 18954-18960.
https://doi.org/10.1074/jbc.271.31.18954 Publication
Researcher Affiliations
- Department of Physiology, James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
MeSH Terms
- Alternative Splicing
- Amino Acid Sequence
- Animals
- Base Sequence
- Cartilage, Articular / metabolism
- DNA Primers / genetics
- DNA, Complementary / genetics
- Dogs
- Fibronectins / chemistry
- Fibronectins / genetics
- Genetic Variation
- Horses
- In Vitro Techniques
- Molecular Sequence Data
- Molecular Structure
- Polymerase Chain Reaction
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Rabbits
- Sequence Homology, Nucleic Acid
- Species Specificity
Citations
This article has been cited 22 times.- Rellmann Y, Eidhof E, Hansen U, Schulte S, Stücker S, Pap T, Dreier R. Extracellular ERp57 promotes fibronectin fibril formation during matrix assembly of articular cartilage. iScience 2025 Dec 19;28(12):114046.
- Pagani S, Maglio M, Sicuro L, Fini M, Giavaresi G, Brogini S. RNA Extraction from Cartilage: Issues, Methods, Tips. Int J Mol Sci 2023 Jan 20;24(3).
- van Hoolwerff M, Tuerlings M, Wijnen IJL, Suchiman HED, Cats D, Mei H, Nelissen RGHH, van der Linden-van der Zwaag HMJ, Ramos YFM, Coutinho de Almeida R, Meulenbelt I. Identification and functional characterization of imbalanced osteoarthritis-associated fibronectin splice variants. Rheumatology (Oxford) 2023 Feb 1;62(2):894-904.
- Thampi P, Liu J, Zeng Z, MacLeod JN. Changes in the appendicular skeleton during metamorphosis in the axolotl salamander (Ambystoma mexicanum). J Anat 2018 Oct;233(4):468-477.
- Chen C, Li R, Ross RS, Manso AM. Integrins and integrin-related proteins in cardiac fibrosis. J Mol Cell Cardiol 2016 Apr;93:162-74.
- Hestand MS, Kalbfleisch TS, Coleman SJ, Zeng Z, Liu J, Orlando L, MacLeod JN. Annotation of the Protein Coding Regions of the Equine Genome. PLoS One 2015;10(6):e0124375.
- Swan AL, Stekel DJ, Hodgman C, Allaway D, Alqahtani MH, Mobasheri A, Bacardit J. A machine learning heuristic to identify biologically relevant and minimal biomarker panels from omics data. BMC Genomics 2015;16 Suppl 1(Suppl 1):S2.
- Scanzello CR, Markova DZ, Chee A, Xiu Y, Adams SL, Anderson G, Zgonis M, Qin L, An HS, Zhang Y. Fibronectin splice variation in human knee cartilage, meniscus and synovial membrane: observations in osteoarthritic knee. J Orthop Res 2015 Apr;33(4):556-62.
- Fels L, Distl O. Identification and validation of quantitative trait loci (QTL) for canine hip dysplasia (CHD) in German Shepherd Dogs. PLoS One 2014;9(5):e96618.
- Bellone RR, Holl H, Setaluri V, Devi S, Maddodi N, Archer S, Sandmeyer L, Ludwig A, Foerster D, Pruvost M, Reissmann M, Bortfeldt R, Adelson DL, Lim SL, Nelson J, Haase B, Engensteiner M, Leeb T, Forsyth G, Mienaltowski MJ, Mahadevan P, Hofreiter M, Paijmans JL, Gonzalez-Fortes G, Grahn B, Brooks SA. Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PLoS One 2013;8(10):e78280.
- Pfahler S, Distl O. Identification of quantitative trait loci (QTL) for canine hip dysplasia and canine elbow dysplasia in Bernese mountain dogs. PLoS One 2012;7(11):e49782.
- Parsons P, Gilbert SJ, Vaughan-Thomas A, Sorrell DA, Notman R, Bishop M, Hayes AJ, Mason DJ, Duance VC. Type IX collagen interacts with fibronectin providing an important molecular bridge in articular cartilage. J Biol Chem 2011 Oct 7;286(40):34986-97.
- Schwarzbauer JE, DeSimone DW. Fibronectins, their fibrillogenesis, and in vivo functions. Cold Spring Harb Perspect Biol 2011 Jul 1;3(7).
- Mienaltowski MJ, Huang L, Frisbie DD, McIlwraith CW, Stromberg AJ, Bathke AC, Macleod JN. Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions. BMC Med Genomics 2009 Sep 14;2:60.
- Brenmoehl J, Miller SN, Hofmann C, Vogl D, Falk W, Schölmerich J, Rogler G. Transforming growth factor-beta 1 induces intestinal myofibroblast differentiation and modulates their migration. World J Gastroenterol 2009 Mar 28;15(12):1431-42.
- Kubota M, Chiba M, Obinata M, Ueda S, Mitani H. Establishment of Periodontal Ligament Cell Lines from Temperature-Sensitive Simian Virus 40 Large T-antigen Transgenic Rats. Cytotechnology 2004 Jan;44(1-2):55-65.
- Mienaltowski MJ, Huang L, Stromberg AJ, MacLeod JN. Differential gene expression associated with postnatal equine articular cartilage maturation. BMC Musculoskelet Disord 2008 Nov 5;9:149.
- Bellone RR, Brooks SA, Sandmeyer L, Murphy BA, Forsyth G, Archer S, Bailey E, Grahn B. Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus). Genetics 2008 Aug;179(4):1861-70.
- Brenmoehl J, Lang M, Hausmann M, Leeb SN, Falk W, Schölmerich J, Göke M, Rogler G. Evidence for a differential expression of fibronectin splice forms ED-A and ED-B in Crohn's disease (CD) mucosa. Int J Colorectal Dis 2007 Jun;22(6):611-23.
- Buratti E, Muro AF, Giombi M, Gherbassi D, Iaconcig A, Baralle FE. RNA folding affects the recruitment of SR proteins by mouse and human polypurinic enhancer elements in the fibronectin EDA exon. Mol Cell Biol 2004 Feb;24(3):1387-400.
- Burton-Wurster N, Gendelman R, Chen H, Gu DN, Tetreault JW, Lust G, Schwarzbauer JE, MacLeod JN. The cartilage-specific (V+C)- fibronectin isoform exists primarily in homodimeric and monomeric configurations. Biochem J 1999 Aug 1;341 ( Pt 3)(Pt 3):555-61.
- Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol 1998 Aug 10;142(3):873-81.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
