What can you know about noncoding RNAs without doing any experiments?
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Transcript of What can you know about noncoding RNAs without doing any experiments?
What can you know about noncoding RNAs
without doing any experiments?
Zasha Weinberg
Laboratory of Ron Breaker
Yale University / HHMI
Data: (Baker, et al., 2012) Drawing: (Weinberg & Breaker, 2011)
Importance of homology
Mammalian HDV ribozyme: poor covariation
(Based on Salehi-Ashtiani, et al., 2006)
Mammalian HDV ribozyme: poor covariation
(Based on Salehi-Ashtiani, et al., 2006)
Mammalian HDV ribozyme: poor covariation
(Based on Salehi-Ashtiani, et al., 2006)
You can know a structure given:
• Covarying mutations
• Few bad mutations
• Homology
• Correct alignment
• Statistical significance
• Michel and Westhof (1990)“Modeling of the three-dimensional architecture of group I catalytic introns based on comparative sequence analysis”
• Pace, Thomas, Woese (1999)“Probing RNA structure, function and history by comparative analysis”
• Weinberg, et al., and Breaker (2010) “Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes.”
Knowing the homologs
• Infernal software search– Knowing: E-value < 10-5
– Thinking: E-value < 10-1
• BLAST search– Knowing: E-value < 10-15 (maybe)– Thinking: E-value < 10-5
• Pattern search, e.g., Rnamotif– No significance statistic given
(Ames, et al., 2010)
Nearby genetic elements can suggest function
RNA-specific tools• Infernal http://infernal.janelia.org• Rfam Database http://rfam.sanger.ac.uk• RNA sequence alignment editors:
– Any text editor– Boulder ALE http://www.microbio.me/boulderale/– RALEE and Emacs
http://personalpages.manchester.ac.uk/staff/sam.griffiths-jones/software/ralee/
• Drawing RNAs– R2R http://www.biomedcentral.com/1471-2105/12/3– XRNA http://rna.ucsc.edu/rnacenter/xrna/– VARNA http://varna.lri.fr/
• Prediction of alignments– WAR Server http://genome.ku.dk/resources/war/– Others: CMfinder, LocaRNA
Summary
Breaker Lab members HHMINIH
Special thanks: mutation and selection
• Know structure by covariation
• Know homologs by E-values
• Know function by nearby genes
Thanks:
Other examples of RNAs and their nearby genes
(Lee, et al., 2010), (Weinberg, et al., 2009)