Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF

I. C. Eperon, D. C. Ireland, R. A. Smith, A. Mayeda, A. R. Krainer

研究成果: Article査読

167 被引用数 (Scopus)

抄録

We have used protection against ribonuclease H to investigate the mechanisms by which U1 small nuclear ribonucleoprotein particles (snRNPs) determine the use of two alternative 5' splice sites. The initial binding of U1 snRNrPs to alternative consensus splice sites was indiscriminate, and on a high proportion of pre-mRNA molecules both sites were occupied simultaneously. When the sites were close, this inhibited splicing. We propose that double occupancy leads to the use of the downstream site for splicing and that this is the cause of the proximity effect seen with strong alternative splice sites. This model predicts that splicing to an upstream site of any strength requires a low affinity of U1 snRNPs for the downstream site. This prediction was tested both by cleaving the 5' end of U1 snRNA and by altering the sequence of the downstream site of an adenovirus E1A gene. The enhancement of downstream 5' splice site use by splicing factor SF2/ASF appears to be mediated by an increase in the strength of U1 snRNP binding to all sites indiscriminately.

本文言語English
ページ(範囲)3607-3617
ページ数11
ジャーナルEMBO Journal
12
9
DOI
出版ステータスPublished - 1993
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)
  • 分子生物学
  • 生化学、遺伝学、分子生物学(全般)
  • 免疫学および微生物学(全般)

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