KnotInFrame: prediction of −1 ribosomal frameshift events

Programmed −1 ribosomal frameshift (−1 PRF) allows for alternative reading frames within one mRNA. First found in several viruses, it is now believed to exist in all kingdoms of life. Strong stimulators for −1 PRF are a heptameric slippery site and an RNA pseudoknot. Here, we present a new algorithm KnotInFrame, for the automatic detection of −1 PRF signals from genomic sequences. It finds the frameshifting stimulators by means of a specialized RNA-pseudoknot folding program, fast enough for genome-wide analyses. Evaluations on known −1 PRF signals demonstrate a high sensitivity.

[1]  T Höchsmann,et al.  Thermodynamic matchers: strengthening the significance of RNA folding energies. , 2006, Computational systems bioinformatics. Computational Systems Bioinformatics Conference.

[2]  E. Westhof,et al.  A novel RNA structural motif in the selenocysteine insertion element of eukaryotic selenoprotein mRNAs. , 1996, RNA.

[3]  E Rivas,et al.  A dynamic programming algorithm for RNA structure prediction including pseudoknots. , 1998, Journal of molecular biology.

[4]  Hisham M. Haddad.  Proceedings of the 2006 ACM symposium on Applied computing , 2006, SAC.

[5]  Robert Giegerich,et al.  Locomotif: from graphical motif description to RNA motif search , 2007, ISMB/ECCB.

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

[7]  Jonathan D Dinman,et al.  PRFdb: A database of computationally predicted eukaryotic programmed -1 ribosomal frameshift signals , 2008, BMC Genomics.

[8]  I. Brierley,et al.  Characterization of the frameshift signal of Edr, a mammalian example of programmed −1 ribosomal frameshifting , 2005, Nucleic acids research.

[9]  Robert Giegerich,et al.  Challenges in the compilation of a domain specific language for dynamic programming , 2006, SAC '06.

[10]  Peter Steffen,et al.  Compiling a domain specific language for dynamic programming , 2006 .

[11]  F. H. D. van Batenburg,et al.  PseudoBase: structural information on RNA pseudoknots , 2001, Nucleic Acids Res..

[12]  A J Herr,et al.  Coupling of open reading frames by translational bypassing. , 2000, Annual review of biochemistry.

[13]  Jonathan D Dinman,et al.  A Three-Stemmed mRNA Pseudoknot in the SARS Coronavirus Frameshift Signal , 2005, PLoS biology.

[14]  D. Ecker,et al.  RNAMotif, an RNA secondary structure definition and search algorithm. , 2001, Nucleic acids research.

[15]  T. Nilsen,et al.  Trans-splicing of nematode premessenger RNA. , 1993, Annual review of microbiology.

[16]  Robert Giegerich,et al.  A discipline of dynamic programming over sequence data , 2004, Sci. Comput. Program..

[17]  Robert Giegerich,et al.  pknotsRG: RNA pseudoknot folding including near-optimal structures and sliding windows , 2007, Nucleic Acids Res..

[18]  Jonathan D. Dinman,et al.  Identification of functional, endogenous programmed −1 ribosomal frameshift signals in the genome of Saccharomyces cerevisiae , 2006, Nucleic acids research.

[19]  L. Brakier-Gingras,et al.  The three transfer RNAs occupying the A, P and E sites on the ribosome are involved in viral programmed -1 ribosomal frameshift , 2007, Nucleic acids research.

[20]  Robert Giegerich,et al.  Versatile and declarative dynamic programming using pair algebras , 2005, BMC Bioinformatics.

[21]  G. W. Beadle,et al.  Genic Control of Biochemical Reactions in Neurospora , 1945, The American Naturalist.

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

[23]  S. Peltz,et al.  Identification of putative programmed -1 ribosomal frameshift signals in large DNA databases. , 1999, Genome research.

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

[25]  S. Napthine,et al.  Ribosomal Pausing at a Frameshifter RNA Pseudoknot Is Sensitive to Reading Phase but Shows Little Correlation with Frameshift Efficiency , 2001, Molecular and Cellular Biology.

[26]  Michel Termier,et al.  Towards a computational model for −1 eukaryotic frameshifting sites , 2003, Bioinform..

[27]  Niles A. Pierce,et al.  A partition function algorithm for nucleic acid secondary structure including pseudoknots , 2003, J. Comput. Chem..

[28]  Sanghoon Moon,et al.  Predicting genes expressed via −1 and +1 frameshifts , 2004, Nucleic acids research.

[29]  David I. Stuart,et al.  A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting , 2006, Nature.

[30]  Robert Giegerich,et al.  Design, implementation and evaluation of a practical pseudoknot folding algorithm based on thermodynamics , 2004, BMC Bioinformatics.