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Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations.

Publication ,  Journal Article
Nissim-Rafinia, M; Chiba-Falek, O; Sharon, G; Boss, A; Kerem, B
Published in: Hum Mol Genet
July 22, 2000

Variable levels of aberrantly spliced cystic fibrosis transmembrane conductance regulator (CFTR ) transcripts were suggested to correlate with variable cystic fibrosis (CF) severity. We studied the effect of the cellular splicing factors, hnRNP A1 and ASF/SF2, and their adenoviral analogues, E4-ORF6 and E4-ORF3, that promote exon skipping and/or exon inclusion, on the splicing pattern of the CFTR mutation 3849+10kb C-->T and the 5T allele. These mutations can lead to cryptic exon inclusion and exon skipping, respectively. Overexpression of the cellular factors promoted exon skipping of pre-mRNA transcribed from minigenes carrying the mutation (p5T or p3849M). This led to a substantial decrease in the level of correctly spliced mRNA transcribed from p5T and generated correctly spliced mRNA transcribed from p3849M that was not found without overexpression of the factors. The viral factor, E4-ORF3, promoted exon inclusion and led to a substantial increase of the correctly spliced mRNA transcribed from the p5T. The factor, E4-ORF6, activated exon skipping and generated correctly spliced mRNA transcribed from p3849M. Thus, overexpression of alternative splicing factors can modulate the splicing pattern of CFTR alleles carrying splicing mutations. These results are important for understanding the mechanism underlying phenotypic variability in CF and other genetic diseases.

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Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

July 22, 2000

Volume

9

Issue

12

Start / End Page

1771 / 1778

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Serine-Arginine Splicing Factors
  • Ribonucleoproteins
  • RNA-Binding Proteins
  • RNA, Messenger
  • RNA, Heterogeneous Nuclear
  • Poly T
  • Nuclear Proteins
  • Mutation
  • Mice
 

Citation

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Nissim-Rafinia, M., Chiba-Falek, O., Sharon, G., Boss, A., & Kerem, B. (2000). Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations. Hum Mol Genet, 9(12), 1771–1778. https://doi.org/10.1093/hmg/9.12.1771
Nissim-Rafinia, M., O. Chiba-Falek, G. Sharon, A. Boss, and B. Kerem. “Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations.Hum Mol Genet 9, no. 12 (July 22, 2000): 1771–78. https://doi.org/10.1093/hmg/9.12.1771.
Nissim-Rafinia M, Chiba-Falek O, Sharon G, Boss A, Kerem B. Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations. Hum Mol Genet. 2000 Jul 22;9(12):1771–8.
Nissim-Rafinia, M., et al. “Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations.Hum Mol Genet, vol. 9, no. 12, July 2000, pp. 1771–78. Pubmed, doi:10.1093/hmg/9.12.1771.
Nissim-Rafinia M, Chiba-Falek O, Sharon G, Boss A, Kerem B. Cellular and viral splicing factors can modify the splicing pattern of CFTR transcripts carrying splicing mutations. Hum Mol Genet. 2000 Jul 22;9(12):1771–1778.
Journal cover image

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

July 22, 2000

Volume

9

Issue

12

Start / End Page

1771 / 1778

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Serine-Arginine Splicing Factors
  • Ribonucleoproteins
  • RNA-Binding Proteins
  • RNA, Messenger
  • RNA, Heterogeneous Nuclear
  • Poly T
  • Nuclear Proteins
  • Mutation
  • Mice