The alternative splicing of fibronectin pre-mRNA is altered during aging and in response to growth factors

V. L. Magnuson, M. Young, D. G. Schattenberg, M. A. Mancini, D. Chen, B. Steffensen, R. J. Klebe

Resultado de la investigación: Articlerevisión exhaustiva

146 Citas (Scopus)

Resumen

The reverse transcription-polymerase chain reaction was used to examine alternative splicing at each of the three fibronectin exons known to undergo alternative splicing, i.e. extra domain A (ED-A), extra domain B (ED-B), and type III connecting sequence (IIICS). Ratios of fibronectin mRNAs with or without a given exon were determined in several rat tissues and human cell lines during aging in vivo and cellular senescence in vitro. We demonstrate that statistically significant shifts in the alternative splicing of fibronectin occur during aging in vivo and in vitro. Since all three alternatively spliced exons are spliced out at a higher frequency in aging tissues and cells, the fibronectin protein produced by old cells should be slightly smaller than that obtained from young cells. The reverse transcription-polymerase chain reaction demonstrates tissue-specific patterns of alternative splicing in several tissues. Whereas fibronectin mRNAs from adult rat tissues were found to range from 0 to 25% ED-A+ and from 0 to 10% ED-B+, fibronectin mRNAs from cultured cell lines were found to be ~50-60% ED-A+ and 15-25% ED-B+. We observed similarity in splicing of fibronectin RNA by the different cultured cell lines obtained from many tissues and attribute this observation to the effect of growth factors. We demonstrate that serum deprivation; placement of cells into primary culture; and growth factors such as transforming growth factor β1, retinoic acid, and 1,25-dihydroxyvitamin D3 can all change the alternative splicing of fibronectin pre-mRNA in the ED-A, ED-B, and type III connecting sequence exons. Possible mechanisms for the regulation of the alternative splicing of fibronectin RNA by growth factors are discussed.

Idioma originalEnglish (US)
Páginas (desde-hasta)14654-14662
Número de páginas9
PublicaciónJournal of Biological Chemistry
Volumen266
N.º22
EstadoPublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Huella

Profundice en los temas de investigación de 'The alternative splicing of fibronectin pre-mRNA is altered during aging and in response to growth factors'. En conjunto forman una huella única.

Citar esto