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You searched for subject:(7SK snRNP). Showing records 1 – 3 of 3 total matches.

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University of California – San Francisco

1. Faust, Tyler Bischoff. Ubiquitin signaling regulates multiple steps in Tat-dependent HIV-1 transcription.

Degree: Biochemistry and Molecular Biology, 2016, University of California – San Francisco

HIV-1 gene expression has provided an excellent model of transcription elongation control. Transcription complexes that assemble at the HIV-1 promoter efficiently initiate transcription but generate paused RNA polymerase II downstream from the start site. The virally encoded Tat protein hijacks P-TEFb to phosphorylate and activate this paused polymerase. Tat binds additional host proteins, but it is unclear if and how they regulate RNAP II elongation. Further, Tat is a particularly small, natively unfolded protein, so it is puzzling how this viral transcription factor is able to bind and redirect the activity of multiple, large host complexes. In this thesis we address these questions by first identifying all Tat amino acids that are essential for its transcriptional activity. The analysis of HIV-1 sequences from infected patients, the activities of an entire set of Tat alanine point mutants, and the replication efficiencies of a randomly mutagenized library of Tat alleles cloned into the virus reveal that Tat and Rev segregate their functional residues in their overlapping coding sequence. Next, a candidate RNAi screen of previously identified novel Tat host interactors reveals that multiple proteins involved in ubiquitin conjugation are essential for Tat activity. Using in vivo purifications and in vitro reconstitution, we show that PJA2, a RING-H2 E3 ubiquitin ligase, directly ubiquitinates Tat. Extensive mutagenesis of Tat and ubiquitin expression constructs reveals both that multiple lysines in Tat can serve as ubiquitin acceptor sites and that multiple lysines in ubiquitin can be used to generate polyubiquitin chains. This immense plasticity of ubiquitin signaling through Tat is likely a way for the virus to encode a transcriptional activity that is robust to a high mutation rate. Using a similar approach, we then demonstrate that Tat hijacks the UBE2O ligase to robustly ubiquitinate specific proteins in the 7SK snRNP. Surprisingly, this ubiquitination occurs in the cytoplasm and functions to remodel the snRNP complex. Remarkably, Tat targets the cytoplasmic 7SK snRNP, releasing P-TEFb from its inhibitor, resulting in nuclear import of the free kinase to activate transcription. This re-localization provides a unique paradigm for P-TEFb control.

Subjects/Keywords: Molecular biology; Biochemistry; 7SK snRNP; HIV-1 Tat; PJA2; Transcription elongation; UBE2O; Ubiquitination

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APA (6th Edition):

Faust, T. B. (2016). Ubiquitin signaling regulates multiple steps in Tat-dependent HIV-1 transcription. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/1r68g5td

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Faust, Tyler Bischoff. “Ubiquitin signaling regulates multiple steps in Tat-dependent HIV-1 transcription.” 2016. Thesis, University of California – San Francisco. Accessed May 20, 2019. http://www.escholarship.org/uc/item/1r68g5td.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Faust, Tyler Bischoff. “Ubiquitin signaling regulates multiple steps in Tat-dependent HIV-1 transcription.” 2016. Web. 20 May 2019.

Vancouver:

Faust TB. Ubiquitin signaling regulates multiple steps in Tat-dependent HIV-1 transcription. [Internet] [Thesis]. University of California – San Francisco; 2016. [cited 2019 May 20]. Available from: http://www.escholarship.org/uc/item/1r68g5td.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Faust TB. Ubiquitin signaling regulates multiple steps in Tat-dependent HIV-1 transcription. [Thesis]. University of California – San Francisco; 2016. Available from: http://www.escholarship.org/uc/item/1r68g5td

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Canterbury

2. Chen R. P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II.

Degree: 2017, University of Canterbury

The release of a paused Pol II depends on the recruitment of P-TEFb. Recent studies showed that both active P-TEFb and inactive P-TEFb (7SK snRNP) can be recruited to the promoter regions of global genes by different mechanisms. Here, we summarize the recent advances on these distinct recruitment mechanisms.

Subjects/Keywords: P-TEFb; 7SK snRNP; Brd4; SEC; KAP1; RNA Pol II; promoter-proximal pausing; transcription elongation; Field of Research::06 - Biological Sciences::0601 - Biochemistry and Cell Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

R, C. (2017). P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II. (Thesis). University of Canterbury. Retrieved from http://hdl.handle.net/10092/15360

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

R, Chen. “P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II.” 2017. Thesis, University of Canterbury. Accessed May 20, 2019. http://hdl.handle.net/10092/15360.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

R, Chen. “P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II.” 2017. Web. 20 May 2019.

Vancouver:

R C. P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II. [Internet] [Thesis]. University of Canterbury; 2017. [cited 2019 May 20]. Available from: http://hdl.handle.net/10092/15360.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

R C. P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II. [Thesis]. University of Canterbury; 2017. Available from: http://hdl.handle.net/10092/15360

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Krueger, Brian. Regulated release of P-Tefb from the 7sk Snrnp.

Degree: PhD, Molecular and Cellular Biology, 2009, University of Iowa

Regulation of transcription elongation by P-TEFb is critical for proper gene expression and cell survival. The cell possesses large quantities of P-TEFb, but the vast majority of it is locked away and inactive in the 7SK snRNP. Since the discovery of the 7SK snRNP, research has been conducted to determine how P-TEFb is released from this complex. The goal of the research presented in this thesis is to better understand how the 7SK snRNP regulates P-TEFb and ultimately, gene expression. This work documents the discovery and characterization of the 7SK stability protein LARP7. LARP7 is is associated with 7SK regardless of the presence of P-TEFb and HEXIM1. Stabilization of 7SK is essential for maintenance of the RNP because loss of LARP7 results in an increase in free P-TEFb and a significant reduction in the amount of 7SK. These results indicate that stabilization of the 7SK snRNP by LARP7 is important for regulating P-TEFb homeostasis. Although P-TEFb was first characterized from Drosophila lysates, the conservation of the 7SK snRNP and the mechanisms regulating P-TEFb inhibition have not been described. Here, the Drosophila melanogaster homologues of LARP7 and 7SK are characterized. These studies show that the system of P-TEFb regulation is similar in flies and this makes Drosophila an attractive model system for studying P-TEFb regulation through embryonic and larval development. Finally, factors and modifications involved in releasing P-TEFb directly are explored. An assay was developed for discovering proteins that can bind to and release P-TEFb from the 7SK snRNP. Use of this assay showed that post-translational modification of the components of the 7SK snRNP do not cause P-TEFb release directly. However, HIV Tat and the C-terminal P-TEFb binding region of the bromodomain containing protein, Brd4, are capable of extracting P-TEFb directly. Most importantly, the release of P-TEFb is followed by a conformational change in 7SK RNA that prevents the continued binding of HEXIM1 to the complex. P-TEFb release from the 7SK snRNP is the result of direct extraction of P-TEFb by viral or cellular proteins, and not post-translational modifications or a competition between HEXIM1 and hnRNP proteins for 7SK binding. Advisors/Committee Members: Price, David H. (supervisor).

Subjects/Keywords: 7SK; 7SK snRNP; Conformational Change; Drosophila; LARP7; P-TEFb; Cell Biology

…of it is inactive in the 7SK snRNP. The 7SK snRNP is composed of the small nuclear RNA 7SK… …the 7SK snRNP, research has been conducted to determine how P-TEFb is released from this… …amount of 7SK. These results indicate that stabilization of the 7SK snRNP by LARP7 is important… …lysates, the conservation of the 7SK snRNP and the mechanisms regulating P-TEFb inhibition have… …release P-TEFb from the 7SK snRNP. Use of this assay showed that phosphorylation… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Krueger, B. (2009). Regulated release of P-Tefb from the 7sk Snrnp. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/839

Chicago Manual of Style (16th Edition):

Krueger, Brian. “Regulated release of P-Tefb from the 7sk Snrnp.” 2009. Doctoral Dissertation, University of Iowa. Accessed May 20, 2019. https://ir.uiowa.edu/etd/839.

MLA Handbook (7th Edition):

Krueger, Brian. “Regulated release of P-Tefb from the 7sk Snrnp.” 2009. Web. 20 May 2019.

Vancouver:

Krueger B. Regulated release of P-Tefb from the 7sk Snrnp. [Internet] [Doctoral dissertation]. University of Iowa; 2009. [cited 2019 May 20]. Available from: https://ir.uiowa.edu/etd/839.

Council of Science Editors:

Krueger B. Regulated release of P-Tefb from the 7sk Snrnp. [Doctoral Dissertation]. University of Iowa; 2009. Available from: https://ir.uiowa.edu/etd/839

.