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Perturbation of transcription elongation influences the fidelity of internal exon inclusion in
 

Summary: Perturbation of transcription elongation influences
the fidelity of internal exon inclusion in
Saccharomyces cerevisiae
KENNETH JAMES HOWE,1
CAROLINE M. KANE,1
and MANUEL ARES, JR.2
1
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
2
Center for the Molecular Biology of RNA, Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz,
Santa Cruz, California 95064, USA
ABSTRACT
Unknown mechanisms exist to ensure that exons are not skipped during biogenesis of mRNA. Studies have connected tran-
scription elongation with regulated alternative exon inclusion. To determine whether the relative rates of transcription elon-
gation and spliceosome assembly might play a general role in enforcing constitutive exon inclusion, we measured exon skipping
for a natural two-intron gene in which the internal exon is constitutively included in the mRNA. Mutations in this gene that
subtly reduce recognition of the intron 1 branchpoint cause exon skipping, indicating that rapid recognition of the first intron
is important for enforcing exon inclusion. To test the role of transcription elongation, we treated cells to increase or decrease
the rate of transcription elongation. Consistent with the "first come, first served" model, we found that exon skipping in vivo
is inhibited when transcription is slowed by RNAP II mutants or when cells are treated with inhibitors of elongation. Expression

  

Source: Ares Jr., Manny - Department of Molecular, Cell, and Developmental Biology, University of California at Santa Cruz

 

Collections: Biology and Medicine