What can you know about noncoding RNAs without

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)

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

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

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. griffi ths-jones/software/ralee/ • Drawing RNAs – R 2 R 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, Loca. RNA

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

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