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

136 Citations (Scopus)

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

Fingerprint

Alleles
Genetic Suppression
Messenger RNA
Mutant Proteins
Introns
Saccharomyces cerevisiae
Adenosine Triphosphatases
Hydrolysis
Nucleotides
Adenosine Triphosphate
Substrates
RNA-dependent ATPase

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

A mechanism to enhance mRNA splicing fidelity : The RNA-dependent ATPase Prp16 governs usage of a discard pathway for aberrant lariat intermediates. / Burgess, Sean M.; Guthrie, Christine.

In: Cell, Vol. 73, No. 7, 02.07.1993, p. 1377-1391.

Research output: Contribution to journalArticle

@article{853218eb4c414b0a84351a42fc1af468,
title = "A mechanism to enhance mRNA splicing fidelity: The RNA-dependent ATPase Prp16 governs usage of a discard pathway for aberrant lariat intermediates",
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.",
author = "Burgess, {Sean M.} and Christine Guthrie",
year = "1993",
month = "7",
day = "2",
doi = "10.1016/0092-8674(93)90363-U",
language = "English (US)",
volume = "73",
pages = "1377--1391",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",

}

TY - JOUR

T1 - A mechanism to enhance mRNA splicing fidelity

T2 - The RNA-dependent ATPase Prp16 governs usage of a discard pathway for aberrant lariat intermediates

AU - Burgess, Sean M.

AU - Guthrie, Christine

PY - 1993/7/2

Y1 - 1993/7/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0027287852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027287852&partnerID=8YFLogxK

U2 - 10.1016/0092-8674(93)90363-U

DO - 10.1016/0092-8674(93)90363-U

M3 - Article

C2 - 8324826

AN - SCOPUS:0027287852

VL - 73

SP - 1377

EP - 1391

JO - Cell

JF - Cell

SN - 0092-8674

IS - 7

ER -