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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.

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What can you know about noncoding RNAs without doing any experiments?

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  1. What can you know about noncoding RNAs without doing any experiments? Zasha Weinberg Laboratory of Ron Breaker Yale University / HHMI

  2. Data: (Baker, et al., 2012) Drawing: (Weinberg & Breaker, 2011)

  3. Importance of homology

  4. Mammalian HDV ribozyme: poor covariation (Based on Salehi-Ashtiani, et al., 2006)

  5. Mammalian HDV ribozyme: poor covariation (Based on Salehi-Ashtiani, et al., 2006)

  6. Mammalian HDV ribozyme: poor covariation (Based on Salehi-Ashtiani, et al., 2006)

  7. You can know a structure given: • Covarying mutations • Few bad mutations • Homology • Correct alignment • Statistical significance

  8. 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.”

  9. 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

  10. Nearby genetic elements can suggest function (Ames, et al., 2010)

  11. 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

  12. Summary • Know structure by covariation • Know homologs by E-values • Know function by nearby genes Thanks: Breaker Lab members HHMI NIH Special thanks: mutation and selection

  13. Other examples of RNAs and their nearby genes (Lee, et al., 2010), (Weinberg, et al., 2009)

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