A unique intronic splicing enhancer controls the inclusion of the agrin Y exon

Nan Wei, Claudia Q. Lin, Edward F. Modafferi, William A. Gomes, Douglas L. Black

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Alternative splicing of the agrin mRNA controls the ability of agrin protein to induce the clustering of acetylcholine receptors at the neuromuscular junction. Using a transfectable reporter gene, we show that one agrin alternative exon, the Y exon, is controlled by a regulatory sequence in the downstream intron. Portions of this intronic sequence have the properties of a splicing enhancer that can activate splicing of a heterologous exon when placed in the intron downstream. The regulatory region is complex in structure, containing several different elements capable of activating splicing. Individual enhancing elements differ in their cell-type specificity, and are not apparently synergistic, as two elements together induce lower splicing than either does separately. Essential nucleotides within these regulatory elements were identified by scanning mutagenesis across the active region. Interestingly, the elements do not appear similar to known intronic splicing enhancer elements. This Y exon enhancer and its components take part in an apparent combinatorial system of control where multiple regulatory elements of varying activity combine to produce a precisely cell-specific exon inclusion. As a major contributor to the regulation of the Y exon, the enhancer ultimately controls the properties of the agrin protein.

Original languageEnglish (US)
Pages (from-to)1275-1288
Number of pages14
JournalRNA
Volume3
Issue number11
StatePublished - Nov 1 1997

Keywords

  • Alternative splicing
  • Neuron
  • Regulatory sequence

ASJC Scopus subject areas

  • Molecular Biology

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    Wei, N., Lin, C. Q., Modafferi, E. F., Gomes, W. A., & Black, D. L. (1997). A unique intronic splicing enhancer controls the inclusion of the agrin Y exon. RNA, 3(11), 1275-1288.