Based on the experimentally determined atomic coordinates for RNA helices and the self-avoiding walks of the P (phosphate) and C4 (carbon) atoms in the diamond lattice for the polynucleotide loop conformations, we derive a set of conformational entropy parameters for RNA pseudoknots. Based on the entropy parameters, we develop a folding thermodynamics model that enables us to compute the sequen...

In this paper, we introduce a combinatorial framework that provides an interpretation of RNA pseudoknot structures as sampling paths of a Markov process. Our results facilitate a variety of applications ranging from the energy-based sampling of pseudoknot structures as well as the ab initio folding via hidden Markov models. Our main result is an algorithm that generates RNA pseudoknot structure...

Telomerase is an RNA-protein complex that includes a unique reverse transcriptase that catalyzes the addition of single-stranded telomere DNA repeats onto the 3' ends of linear chromosomes using an integral telomerase RNA (TR) template. Vertebrate TR contains the template/pseudoknot (t/PK) and CR4/5 domains required for telomerase activity in vitro. All vertebrate pseudoknots include two subdom...

Dual graphs have been applied to model RNA secondary structures with pseudoknots, or intertwined base pairs. In this paper we present a linear-time algorithm to partition dual graphs into topological components called blocks and determine whether each block contains a pseudoknot or not. We show that a block contains a pseudoknot if and only if the block has a vertex of degree 3 or more; this ch...

We developed a new method that can profile and efficiently search for pseudoknot structures in noncoding RNA genes. It profiles interleaving stems in pseudoknot structures with independent Covariance Model (CM) components. The statistical alignment score for searching is obtained by combining the alignment scores from all CM components. Our experiments show that the model can achieve excellent ...

Most ab initio pseudoknot predicting methods provide very few folding scenarios for a given RNA sequence and have low sensitivities. RNA researchers, in many cases, would rather sacrifice the specificity for a much higher sensitivity for pseudoknot detection. In this study, we introduce the Pseudoknot Local Motif Model and Dynamic Partner Sequence Stacking (PLMM_DPSS) algorithm which predicts a...

Pseudoknots are an essential feature of RNA tertiary structures. Simple H-type pseudoknots have been studied extensively in terms of biological functions, computational prediction, and energy models. Intramolecular kissing hairpins are a more complex and biologically important type of pseudoknot in which two hairpin loops form base pairs. They are hard to predict using free energy minimization ...

Autosomal dominant dyskeratosis congenita (DKC), as well as aplastic anemia, has been linked to mutations in the RNA component of telomerase, the ribonucleoprotein responsible for telomere maintenance. Here we examine the effect of the DKC mutations on the structure and stability of human telomerase RNA pseudoknot and CR7 domains by using NMR and thermal melting. The CR7 domain point mutation d...

The large double-stranded RNA of the Saccharomyces cerevisiae (yeast) virus has two large overlapping open reading frames on the plus strand, one of which is translated via a -1 ribosomal frameshift. Sequences including the overlapping region, placed in novel contexts, can direct ribosomes to make a -1 frameshift in wheat germ extract, Escherichia coli and S. cerevisiae. This sequence includes ...

The pseudoknot domain is a functionally crucial part of telomerase RNA and influences the activity and stability of the ribonucleoprotein complex. Autosomal dominant dyskeratosis congenita (DKC) is an inherited disease that is linked to mutations in telomerase RNA and impairs telomerase function. In this paper, we present a computational prediction of the influence of two base DKC mutations on ...