The analyses of the biological role of transcription errors will promote our understanding of substrate specificity of RNA polymerase. RNA polymerase errors also have a major impact on transcription pausing and arrest. Better understanding he mechanisms of transcription pausing and errors and their proofreading in living cells will provide additional insights into the side effects of the clinically relevant NTP analogues. We dissected one of the basic mechanisms for transcription pausing involving slow translocation of RNA polymerase along DNA regulated by the length of RNA-DNA hybrid in the elongation complex. This mechanism is shared by prokaryotic and eukaryotic RNA polymerases. Our new findings may be expanded to address the interconnection of transcription elongation, co-transcriptional splicing, and termination.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010795-12
Application #
9779713
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Imashimizu, Masahiko; Takahashi, Hiroki; Oshima, Taku et al. (2015) Visualizing translocation dynamics and nascent transcript errors in paused RNA polymerases in vivo. Genome Biol 16:98
Penno, Christophe; Sharma, Virag; Coakley, Arthur et al. (2015) Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in common with intrinsic terminators. Proc Natl Acad Sci U S A 112:E1984-93
Parks, Adam R; Court, Carolyn; Lubkowska, Lucyna et al. (2014) Bacteriophage ? N protein inhibits transcription slippage by Escherichia coli RNA polymerase. Nucleic Acids Res 42:5823-9
Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku et al. (2014) Transcription elongation: Heterogeneous tracking of RNA polymerase and its biological implications. Transcription 5:
Afonin, Kirill A; Kasprzak, Wojciech K; Bindewald, Eckart et al. (2014) In silico design and enzymatic synthesis of functional RNA nanoparticles. Acc Chem Res 47:1731-41
Vitiello, Christal L; Kireeva, Maria L; Lubkowska, Lucyna et al. (2014) Coliphage HK022 Nun protein inhibits RNA polymerase translocation. Proc Natl Acad Sci U S A 111:E2368-75
Afonin, Kirill A; Desai, Ravi; Viard, Mathias et al. (2014) Co-transcriptional production of RNA-DNA hybrids for simultaneous release of multiple split functionalities. Nucleic Acids Res 42:2085-97
Imashimizu, Masahiko; Kashlev, Mikhail (2014) Unveiling translocation intermediates of RNA polymerase. Proc Natl Acad Sci U S A 111:7507-8
Ishibashi, Toyotaka; Dangkulwanich, Manchuta; Coello, Yves et al. (2014) Transcription factors IIS and IIF enhance transcription efficiency by differentially modifying RNA polymerase pausing dynamics. Proc Natl Acad Sci U S A 111:3419-24
Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku et al. (2014) Transcription elongation. Heterogeneous tracking of RNA polymerase and its biological implications. Transcription 5:e28285

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