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)
