lecture7_S2009

lecture7_S2009 - 18.417: Introduction to Computational...

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1 8 . 4 1 7 : I n t r o d u c t i o n t o C o m p u t a t i o n a l M o l e c u l a r B i o l o g y R N A - R N A i n t e r a c t i o n p r e d i c t i o n J e r o m e W a l d i s p u h l D e p a r t m e n t o f M a t h e m a t i c s , M I T S l i d e s f r o m I v o H o f a c k e r ( U n i v e r s i t y o f V i e n n a )
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Motivation Experimental and bioinformatical methods Fnd novel ncRNAs en masse Give no hint as to the function of these novel ncRNAs ±unctional characterization of ncRNAs is difficult and slow Most ncRNAs function through interaction with other RNAs IdentiFcation of interaction partners is the easiest approach to learn about possible functions Most obvious in the case of miRNA target prediction
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Well known Examples of RNA-RNA Interaction micro RNAs regulate mRNA translation snoRNAs guide methylation and pseudouridylation of rRNA some well studied bacterial examples RyhB is transcribed under low Fe, binds several mRNA of Fe binding proteins (sdh, sodB) and leads to mRNA degradation GadY interacts with the 3’ UTR of GadX and inhibits its degradation DsrA is expressed at low temperatures and stimulates the translation of RpoS a translational regulator OxyS is expressed under oxidative stress and inhibits translation of its targets RpoS and flhA T-box motifs bind uncharged tRNAs to control transcription of aminoacyl synthetases
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Interaction of OxyS and fhla Binding of OxyS to fhlA mRNA makes the ribosome binding site (start codon) inaccessible
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Transcriptional control by T-box Motifs Concentration of un-charged tRNAs controls transcription of its aminoacyl synthetase
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Challenges Few well-studied examples Energetics of many interaction motifs are unknown Length of the interacting region is often quite small Binding is a concentration dependent process Folding kinetics rather than thermodynamics may play a role A single small RNA may have many targets RNA chaperones such as Hfq may be required for binding ncRNAs often act within RNPs, what’s the influence of the protein?
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Overview of Prediction Strategies Co-folding by concatenation of two sequences, e.g. RNAcofold , pairfold , DINAMELT , Nupack Co-folding with pseudoknot-like structures, IRIS Using only inter-molecular interaction, i.e. assume that both molecules are unstructured by themselves. RNAhybrid , RNAduplex , codeRNAplex Combine interaction search with accessibility calculations. RNAup , RNAplfold + RNAplex , oligowalk
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Simple Co-folding of two RNAs Poor man’s approach to cofolding: Concatenate two RNAs using a short linker Use conventional folding programs such as mfold Proper way: Use modiFed folding algorithm that keeps track of the break between the strands Any loop containing the break point is treated specially.
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This note was uploaded on 06/16/2011 for the course MATH 18.417 taught by Professor Jérômewaldispühl during the Spring '11 term at MIT.

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lecture7_S2009 - 18.417: Introduction to Computational...

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