Adventures in time and space: splicing efficiency and RNA polymerase II elongation rate.
Control of pre-mRNA splicing is a critical part of the eukaryotic gene expression process. Extensive evidence indicates that transcription and splicing are spatiotemporally coordinated and that most splicing events occur co-transcriptionally. A kinetic coupling model has been proposed in metazoans to describe how changing RNA Polymerase II (RNAPII) elongation rate can impact which alternative splice sites are used. In Saccharomyces cerevisiae, in which most spliced genes have only a single intron and splice sites adhere to a strong consensus sequence, we recently observed that splicing efficiency was sensitive to mutations in RNAPII that increase or decrease its elongation rate. Our data revealed that RNAPII speed and splicing efficiency are generally anti-correlated: at many genes, increased elongation rate caused decreased splicing efficiency, while decreased elongation rate increased splicing efficiency. An improved splicing phenotype was also observed upon deletion of SUB1, a condition in which elongation rate is slowed. We discuss these data in the context of a growing field and expand the kinetic coupling model to apply to both alternative splicing and splicing efficiency.
Department of Biochemistry and Biophysics; University of California; San Francisco, CA USA.
Erica A
EA
Moehle
Department of Cellular and Molecular Pharmacology; University of California; San Francisco, CA USA; California Institute for Quantitative Biosciences; QB3; San Francisco, CA USA.
Hannes
H
Braberg
Department of Cellular and Molecular Pharmacology; University of California; San Francisco, CA USA; California Institute for Quantitative Biosciences; QB3; San Francisco, CA USA; J. David Gladstone Institutes; San Francisco, CA USA.
Nevan J
NJ
Krogan
Department of Biochemistry and Biophysics; University of California; San Francisco, CA USA.
Christine
C
Guthrie
D006801:Humans; D007700:Kinetics; D012319:RNA Polymerase II / Q000378:metabolism*; D012326:RNA Splicing / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D014158:Transcription, Genetic
D012319:RNA Polymerase II
RNA polymerase II; elongation rate; kinetic coupling; splicing; splicing efficiency