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)