Inhibition of fibrillin 1 expression using U1 snRNA as a vehicle for the presentation of antisense targeting sequence

Robert A. Montgomery, Harry C. Dietz

Research output: Contribution to journalArticle

Abstract

This study examines whether the mimicking of selected properties of naturally occurring antisense RNAs in prokaryotes allows efficient inhibition of gene expression by in situ-expressed recombinant molecules in mammalian cells. Prokaryotic regulatory transcripts are expressed at high levels and have hairpin structures at their termini, features reminiscent of small nuclear RNAs (snRNAs) which are abundant and stable in the nucleus of all mammalian cells. A sequence complementary to fibrillin-1 (FBN1) mRNA, interrupted in its center by a hammerhead ribozyme, was substituted for the Sm protein binding site between the stem-loop structures of U1 snRNA. Expression of the chimeric antisense RNA resulted in dramatic inhibition of expression of fibrillin-1 message and protein in stably transfected cultured cells. The inhibitory effect was localized to the nucleus. The biological properties of U1 snRNA may provide a widely applicable vehicle for the in vivo delivery of antisense targeting sequences.

Original languageEnglish (US)
Pages (from-to)519-525
Number of pages7
JournalHuman molecular genetics
Volume6
Issue number4
DOIs
StatePublished - Apr 1 1997

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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