A mechanism to enhance mRNA splicing fidelity: The RNA-dependent ATPase Prp16 governs usage of a discard pathway for aberrant lariat intermediates

Sean M. Burgess, Christine Guthrie

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

PRP16 encodes an RNA-dependent ATPase required for the second step of mRNA splicing in S. cerevisiae. We have isolated seven alleles of PRP16 that, like the original allele prp16-1, allow splicing of introns with a mutant branch site (UACUAAC to UACUACC), by forming lariat intermediates at the mutant C nucleotide. Every suppressor mutation maps to the region of PRP16 common to RNA-dependent ATPases. We purified three of the mutant proteins and found that all exhibit reduced ATPase activity, as does Prp16-1. An in vivo analysis of the steady-state levels of the splicing intermediates and products provides evidence for a pathway, under the genetic control of PRP16, to discard incorrectly branched substrates. We propose that decreasing the rate of ATP hydrolysis by Prp16 allows aberrantly formed lariat intermediates more time to proceed through the productive rather than the discard branch of this pathway.

Original languageEnglish (US)
Pages (from-to)1377-1391
Number of pages15
JournalCell
Volume73
Issue number7
DOIs
StatePublished - Jul 2 1993

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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