Co-transcriptional splicing of pre-messenger RNAs: Considerations for the mechanism of alternative splicing

Aaron C. Goldstrohm, Arno L. Greenleaf, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Nascent transcripts are the true substrates for many splicing events in mammalian cells. In this review we discuss transcription, splicing, and alternative splicing in the context of co-transcriptional processing of pre-mRNA. The realization that splicing occurs co-transcriptionally requires two important considerations: First, the cis-acting elements in the splicing substrate are synthesized at different times in a 5′ to 3′ direction. This dynamic view of the substrate implies that in a 100 kb intron the 5′ splice site will be synthesized as much as an hour before the 3′ splice site. Second, the transcription machinery and the splicing machinery, which are both complex and very large, are working in close proximity to each other. It is therefore likely that these two macromolecular machines interact, and recent data supporting this notion is discussed. We propose a model for co-transcriptional pre-mRNA processing that incorporates the concepts of splice site-tethering and dynamic exon definition. Also, we present a dynamic view of the alternative splicing of FGF-R2 and suggest that this view could be generally applicable to many regulated splicing events.

Original languageEnglish (US)
Pages (from-to)31-47
Number of pages17
JournalGene
Volume277
Issue number1-2
DOIs
StatePublished - Oct 17 2001
Externally publishedYes

Fingerprint

RNA Splicing
RNA Splice Sites
RNA Precursors
Alternative Splicing
Introns
Exons
Direction compound

Keywords

  • Dynamic exon definition
  • Pre-mRNA splicing
  • Splice site-tethering
  • Transcription

ASJC Scopus subject areas

  • Genetics

Cite this

Co-transcriptional splicing of pre-messenger RNAs : Considerations for the mechanism of alternative splicing. / Goldstrohm, Aaron C.; Greenleaf, Arno L.; Garcia-Blanco, Mariano.

In: Gene, Vol. 277, No. 1-2, 17.10.2001, p. 31-47.

Research output: Contribution to journalArticle

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