Transcription elongation rate affects nascent histone pre-mRNA folding and 3′ end processing
- Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, Colorado 80045, USA
- Corresponding author: david.bentley{at}ucdenver.edu
Abstract
Transcription elongation rate influences cotranscriptional pre-mRNA maturation, but how such kinetic coupling works is poorly understood. The formation of nonadenylated histone mRNA 3′ ends requires recognition of an RNA structure by stem–loop-binding protein (SLBP). We report that slow transcription by mutant RNA polymerase II (Pol II) caused accumulation of polyadenylated histone mRNAs that extend past the stem–loop processing site. UV irradiation, which decelerates Pol II elongation, also induced long poly(A)+ histone transcripts. Inhibition of 3′ processing by slow Pol II correlates with failure to recruit SLBP to histone genes. Chemical probing of nascent RNA structure showed that the stem–loop fails to fold in transcripts made by slow Pol II, thereby explaining the absence of SLBP and failure to process 3′ ends. These results show that regulation of transcription speed can modulate pre-mRNA processing by changing nascent RNA structure and suggest a mechanism by which alternative processing could be controlled.
Keywords
- transcription elongation rate
- cotranscriptional RNA folding
- histone mRNA 3′ end processing
- stem–loop binding protein
- kinetic coupling
Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.310896.117.
- Received December 15, 2017.
- Accepted January 23, 2018.
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