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Genetic Dissection of the RNA Polymerase II Transcription Cycle

Shao-Pei Chou, Adriana K. Alexander, Edward J. Rice, Lauren A Choate, Paula E Cohen, View ORCID ProfileCharles G. Danko
doi: https://doi.org/10.1101/2021.05.23.445279
Shao-Pei Chou
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Adriana K. Alexander
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
2Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Edward J. Rice
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Lauren A Choate
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Paula E Cohen
2Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Charles G. Danko
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
2Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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  • ORCID record for Charles G. Danko
  • For correspondence: dankoc@gmail.com
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Abstract

How DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here we used naturally occurring genetic variation in F1 hybrid mice to explore how DNA sequence differences affect the genome-wide distribution of Pol II. We measured the position and orientation of Pol II in eight organs collected from heterozygous F1 hybrid mice using ChRO-seq. Our data revealed a strong genetic basis for the precise coordinates of transcription initiation and promoter proximal pause, allowing us to redefine molecular models of core transcriptional processes. Our results implicate the strength of base pairing between A-T or G-C dinucleotides as key determinants to the position of Pol II initiation and pause. We report evidence that initiation site selection follows a stochastic process similar to brownian motion along the DNA template. We found widespread differences in the position of transcription termination, which impact the primary structure and stability of mature mRNA. Finally, we report evidence that allelic changes in transcription often affect mRNA and ncRNA expression across broad genomic domains. Collectively, we reveal how DNA sequences shape core transcriptional processes at single nucleotide resolution in mammals.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • We have completed extensive revisions from three reviewers. We are sending this version of the manuscript back out for peer review.

Copyright 
The copyright holder has placed this preprint in the Public Domain. It is no longer restricted by copyright. Anyone can legally share, reuse, remix, or adapt this material for any purpose without crediting the original authors.
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Posted March 07, 2022.
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Genetic Dissection of the RNA Polymerase II Transcription Cycle
Shao-Pei Chou, Adriana K. Alexander, Edward J. Rice, Lauren A Choate, Paula E Cohen, Charles G. Danko
bioRxiv 2021.05.23.445279; doi: https://doi.org/10.1101/2021.05.23.445279
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Genetic Dissection of the RNA Polymerase II Transcription Cycle
Shao-Pei Chou, Adriana K. Alexander, Edward J. Rice, Lauren A Choate, Paula E Cohen, Charles G. Danko
bioRxiv 2021.05.23.445279; doi: https://doi.org/10.1101/2021.05.23.445279

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