Transcription elongation by RNA polymerases (RNAPs) is functionally connected with DNA replication, repair, and chromatin organization, and thus affects the overall integrity and organization of the genome. Taken together with the central role of the post-initiation events in regulation of mRNA synthesis, the complexity of the network involving RNAP suggests that the changes in the transcription elongation rate, fidelity and the propensity of RNAP to undergo transcription arrest has a broad impact on cell physiology. The analyses of the biological role of transcription fidelity will promote our understanding of RNAP substrate specificity. It will provide additional insights into the mechanisms and side effects of the clinically relevant NTP analogues. In addition, transcription fidelity might be connected to the transcription-coupled DNA repair. Specifically, we have recently established that the ability of yeast/mammalian Pol II to recognize the lesion in the DNA is determined by the mechanisms similar to those regulating cognate NTP substrate selection. The scope of the research may be expanded to address the interconnection of transcription elongation and other DNA transactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010795-08
Application #
8937848
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
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
Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku et al. (2014) Transcription elongation: Heterogeneous tracking of RNA polymerase and its biological implications. Transcription 5:
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
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
Imashimizu, Masahiko; Kashlev, Mikhail (2014) Unveiling translocation intermediates of RNA polymerase. Proc Natl Acad Sci U S A 111:7507-8
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
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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