IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions

Motivation: During the last few years, several new small regulatory RNAs (sRNAs) have been discovered in bacteria. Most of them act as post-transcriptional regulators by base pairing to a target mRNA, causing translational repression or activation, or mRNA degradation. Numerous sRNAs have already been identified, but the number of experimentally verified targets is considerably lower. Consequently, computational target prediction is in great demand. Many existing target prediction programs neglect the accessibility of target sites and the existence of a seed, while other approaches are either specialized to certain types of RNAs or too slow for genome-wide searches. Results: We introduce INTARNA, a new general and fast approach to the prediction of RNA–RNA interactions incorporating accessibility of target sites as well as the existence of a user-definable seed. We successfully applied INTARNA to the prediction of bacterial sRNA targets and determined the exact locations of the interactions with a higher accuracy than competing programs. Availability: http://www.bioinf.uni-freiburg.de/Software/ Contact: IntaRNA@informatik.uni-freiburg.de Supplementary information: Supplementary data are available at Bioinformatics online.

[1]  J. Vogel,et al.  Target identification of small noncoding RNAs in bacteria. , 2007, Current opinion in microbiology.

[2]  M. Zuker,et al.  Prediction of hybridization and melting for double-stranded nucleic acids. , 2004, Biophysical journal.

[3]  Michael Zuker,et al.  Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information , 1981, Nucleic Acids Res..

[4]  Peter F. Stadler,et al.  Local RNA base pairing probabilities in large sequences , 2006, Bioinform..

[5]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

[6]  Stefan L Ameres,et al.  Molecular Basis for Target RNA Recognition and Cleavage by Human RISC , 2007, Cell.

[7]  M. Kozak,et al.  Regulation of translation via mRNA structure in prokaryotes and eukaryotes. , 2005, Gene.

[8]  Michael Zuker,et al.  DINAMelt web server for nucleic acid melting prediction , 2005, Nucleic Acids Res..

[9]  Georg Sczakiel,et al.  The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides. , 2003, Nucleic acids research.

[10]  N. Majdalani,et al.  Small non‐coding RNAs, co‐ordinators of adaptation processes in Escherichia coli: the RpoS paradigm , 2003, Molecular microbiology.

[11]  S. Gottesman,et al.  A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Giegerich,et al.  Fast and effective prediction of microRNA/target duplexes. , 2004, RNA.

[13]  J. Vogel,et al.  The Small RNA IstR Inhibits Synthesis of an SOS-Induced Toxic Peptide , 2004, Current Biology.

[14]  L. Argaman,et al.  fhlA repression by OxyS RNA: kissing complex formation at two sites results in a stable antisense-target RNA complex. , 2000, Journal of molecular biology.

[15]  Brian Tjaden,et al.  TargetRNA: a tool for predicting targets of small RNA action in bacteria , 2008, Nucleic Acids Res..

[16]  Chi Yu Chan,et al.  Effect of target secondary structure on RNAi efficiency. , 2007, RNA.

[17]  Serafim Batzoglou,et al.  CONTRAfold: RNA secondary structure prediction without physics-based models , 2006, ISMB.

[18]  L. Bossi,et al.  A small RNA downregulates LamB maltoporin in Salmonella , 2007, Molecular microbiology.

[19]  D. Pervouchine.  IRIS: intermolecular RNA interaction search. , 2004, Genome informatics. International Conference on Genome Informatics.

[20]  Jan Krüger,et al.  RNAhybrid: microRNA target prediction easy, fast and flexible , 2006, Nucleic Acids Res..

[21]  A. Condon,et al.  Secondary structure prediction of interacting RNA molecules. , 2005, Journal of molecular biology.

[22]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[23]  J. Vogel,et al.  A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites. , 2007, Genes & development.

[24]  D. Touati,et al.  Hfq, a new chaperoning role: binding to messenger RNA determines access for small RNA regulator , 2004, The EMBO journal.

[25]  Hakim Tafer,et al.  RNAplex: a fast tool for RNA-RNA interaction search , 2008, Bioinform..

[26]  N. Delihas,et al.  Secondary structures of Escherichia coli antisense micF RNA, the 5'-end of the target ompF mRNA, and the RNA/RNA duplex. , 1995, Biochemistry.

[27]  J. McCaskill.  The equilibrium partition function and base pair binding probabilities for RNA secondary structure , 1990, Biopolymers.

[28]  G. Storz,et al.  Target prediction for small, noncoding RNAs in bacteria , 2006, Nucleic acids research.

[29]  D. Chang,et al.  Using a hydrogen-bond index to predict the gene-silencing efficiency of siRNA based on the local structure of mRNA , 2017, 1710.07413.

[30]  Todd A. Anderson,et al.  Computational identification of microRNAs and their targets , 2006, Comput. Biol. Chem..

[31]  Süleyman Cenk Sahinalp,et al.  taveRNA: a web suite for RNA algorithms and applications. , 2007, Nucleic acids research.

[32]  Michael Kertesz,et al.  The role of site accessibility in microRNA target recognition , 2007, Nature Genetics.

[33]  Rolf Backofen,et al.  Variations on RNA folding and alignment: lessons from Benasque , 2007, Journal of mathematical biology.

[34]  G. Storz.  An Expanding Universe of Noncoding RNAs , 2002, Science.

[35]  G. Storz,et al.  Controlling mRNA stability and translation with small, noncoding RNAs. , 2004, Current opinion in microbiology.

[36]  S. Gottesman.  Micros for microbes: non-coding regulatory RNAs in bacteria. , 2005, Trends in genetics : TIG.

[37]  N. Rajewsky.  microRNA target predictions in animals , 2006, Nature Genetics.

[38]  J. Sabina,et al.  Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. , 1999, Journal of molecular biology.

[39]  Volker Patzel,et al.  Selecting effective siRNAs based on guide RNA structure , 2006, Nature Protocols.

[40]  Phillip D. Zamore,et al.  RNA Interference , 2000, Science.

[41]  G. Storz,et al.  MicC, a Second Small-RNA Regulator of Omp Protein Expression in Escherichia coli , 2004, Journal of bacteriology.

[42]  Kaizhong Zhang,et al.  RNA-RNA Interaction Prediction and Antisense RNA Target Search , 2006, J. Comput. Biol..

[43]  Dang D. Long,et al.  Potent effect of target structure on microRNA function , 2007, Nature Structural &Molecular Biology.

[44]  Dieter Haas,et al.  A guide to small RNAs in microorganisms , 2007 .

[45]  J. Vogel,et al.  Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA. , 2005, Genes & development.

[46]  M. Hiller,et al.  Using RNA secondary structures to guide sequence motif finding towards single-stranded regions , 2006, Nucleic acids research.

[47]  J. Vogel,et al.  Two Seemingly Homologous Noncoding RNAs Act Hierarchically to Activate glmS mRNA Translation , 2008, PLoS biology.

[48]  Phillip D. Zamore,et al.  Ribo-gnome: The Big World of Small RNAs , 2005, Science.

[49]  H. Aiba,et al.  Base‐pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq , 2006, Molecular microbiology.

[50]  G. Hannon.  RNA interference : RNA , 2002 .

[51]  Walter Fontana,et al.  Fast folding and comparison of RNA secondary structures , 1994 .

[52]  P. Valentin‐Hansen,et al.  Spot 42 RNA mediates discoordinate expression of the E. coli galactose operon. , 2002, Genes & development.

[53]  E. Wagner,et al.  Dealing with stable structures at ribosome binding sites: Bacterial translation and ribosome standby , 2007, RNA biology.

[54]  Mladen A. Vouk,et al.  Predicting Shine–Dalgarno Sequence Locations Exposes Genome Annotation Errors , 2006, PLoS Comput. Biol..

[55]  John G Doench,et al.  Specificity of microRNA target selection in translational repression. , 2004, Genes & development.

[56]  Peter F. Stadler,et al.  Translational Control by RNA-RNA Interaction: Improved Computation of RNA-RNA Binding Thermodynamics , 2008, BIRD.

[57]  Isaac Bentwich.  Available online , 2005 .

[58]  Peter F. Stadler,et al.  Partition function and base pairing probabilities of RNA heterodimers , 2006, Algorithms for Molecular Biology.

[59]  N. Delihas,et al.  Annotation and evolutionary relationships of a small regulatory RNA gene micF and its target ompF in Yersinia species , 2003, BMC Microbiology.