Regulated transcription is one of the principle mechanisms to alter gene expression in response to environmental stimuli. Intensive study over more than 3 decades has provided a detailed understanding of the transcriptional machinery as well as many of the signals to which it responds. A novel mechanism for altering transcription, which uses the RNA-regulator 6S RNA, recently has been discovered. Therefore, a detailed understanding of the role of 6S RNA in transcriptional regulation is instrumental for full comprehension of how appropriate cellular gene expression is maintained. Cells with altered 6S RNA levels are decreased in their ability to survive in stationary phase, indicating 6S RNA has a major impact on cell physiology. Many small RNAs in bacteria are utilized to optimize cellular responses to unfavorable nutritional or chemical environments through post-transcriptional regulation of gene expression. 6S RNA expands this list to include regulation in response to late stationary phase, as well as to include a unique method of regulation at the level of transcription. This proposal focuses on answering three questions regarding 6S RNA function and activity: 1. How global are 6S RNA effects on gene expression which will be addressed by identification of the 6S RNA regulon; 2. What are the physiological consequences of 6S RNA mediated changes in gene expression which will be addressed through genetic analysis of phenotypes associated with loss of 6S RNA; 3. How 6S RNA changes the transcriptional machinery and its activity, which will be addressed through biochemical approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067955-03
Application #
6890953
Study Section
Special Emphasis Panel (ZRG1-MBC-2 (01))
Program Officer
Anderson, James J
Project Start
2003-05-01
Project End
2008-04-30
Budget Start
2005-05-01
Budget End
2006-04-30
Support Year
3
Fiscal Year
2005
Total Cost
$249,709
Indirect Cost
Name
University of Wisconsin Madison
Department
Microbiology/Immun/Virology
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Wassarman, Karen M (2018) 6S RNA, a Global Regulator of Transcription. Microbiol Spectr 6:
Chen, James; Wassarman, Karen M; Feng, Shili et al. (2017) 6S RNA Mimics B-Form DNA to Regulate Escherichia coli RNA Polymerase. Mol Cell 68:388-397.e6
Cavanagh, Amy T; Wassarman, Karen M (2014) 6S RNA, a global regulator of transcription in Escherichia coli, Bacillus subtilis, and beyond. Annu Rev Microbiol 68:45-60
Cabrera-Ostertag, Ignacio J; Cavanagh, Amy T; Wassarman, Karen M (2013) Initiating nucleotide identity determines efficiency of RNA synthesis from 6S RNA templates in Bacillus subtilis but not Escherichia coli. Nucleic Acids Res 41:7501-11
Cavanagh, Amy T; Wassarman, Karen M (2013) 6S-1 RNA function leads to a delay in sporulation in Bacillus subtilis. J Bacteriol 195:2079-86
Cavanagh, Amy T; Sperger, Jamie M; Wassarman, Karen M (2012) Regulation of 6S RNA by pRNA synthesis is required for efficient recovery from stationary phase in E. coli and B. subtilis. Nucleic Acids Res 40:2234-46
Storz, Gisela; Vogel, Jörg; Wassarman, Karen M (2011) Regulation by small RNAs in bacteria: expanding frontiers. Mol Cell 43:880-91
Cavanagh, Amy T; Chandrangsu, Pete; Wassarman, Karen M (2010) 6S RNA regulation of relA alters ppGpp levels in early stationary phase. Microbiology 156:3791-800
Klocko, Andrew D; Wassarman, Karen M (2009) 6S RNA binding to Esigma(70) requires a positively charged surface of sigma(70) region 4.2. Mol Microbiol 73:152-64
Cavanagh, Amy T; Klocko, Andrew D; Liu, Xiaochun et al. (2008) Promoter specificity for 6S RNA regulation of transcription is determined by core promoter sequences and competition for region 4.2 of sigma70. Mol Microbiol 67:1242-56

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