what can you know about noncoding rnas without doing any experiments? zasha weinberg laboratory of...
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What can you know about noncoding RNAs
without doing any experiments?
Zasha WeinbergLaboratory of Ron Breaker
Yale University / HHMI
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Data: (Baker, et al., 2012) Drawing: (Weinberg & Breaker, 2011)
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Importance of homology
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Mammalian HDV ribozyme: poor covariation
(Based on Salehi-Ashtiani, et al., 2006)
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Mammalian HDV ribozyme: poor covariation
(Based on Salehi-Ashtiani, et al., 2006)
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Mammalian HDV ribozyme: poor covariation
(Based on Salehi-Ashtiani, et al., 2006)
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You can know a structure given:
• Covarying mutations• Few bad mutations• Homology• Correct alignment• Statistical significance
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• 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.”
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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
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(Ames, et al., 2010)
Nearby genetic elements can suggest function
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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
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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:
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Other examples of RNAs and their nearby genes
(Lee, et al., 2010), (Weinberg, et al., 2009)