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.
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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 -