RNA structural segmentation. (1/179)

We describe several dynamic programming segmentation algorithms to segment RNA secondary and tertiary structures into distinct domains. For this purpose, we consider fitness functions that variously depend on (i) base pairing probabilities in the Boltzmann low energy ensemble of structures, (ii) contact maps inferred from 3-dimensional structures, and (iii) Voronoi tessellation computed from 3-dimensional structures. Segmentation algorithms include a direct dynamic programming method, previously discovered by Bellman and by Finkelstein and Roytberg, as well as two novel algorithms - a parametric algorithm to compute the optimal segmentation into k classes, for each value k, and an algorithm that simultaneously computes the optimal segmentation of all subsegments. Since many non-coding RNA gene finders scan the genome by a moving window method, reporting high-scoring windows, we apply structural segmentation to determine the most likely 5' and 3' boundaries of precursor microRNAs. When tested on all precursor microRNAs of length at most 100 nt from the Rfam database, benchmarking studies indicate that segmentation determines the 5' boundary with discrepancy (absolute value of difference between predicted and real boundaries) having mean -0.640 (stdev 15.196) and the 3' boundary with discrepancy having mean -0.266 (stdev. 17.415). This yields a sensitivity of 0.911 and positive predictive value of 0.906 for determination of exact boundaries of precursor microRNAs within a window of approximately 900 nt. Additionally, by comparing the manual segmentation of Jaeger et al. with our optimal structural segmentation of 16S and 16S-like rRNA of E. coli, rat mitochondria, Halobacterium volcanii, and Chlamydomonas reinhardii chloroplast into 4 segments, we establish the usefulness of (automated) structural segmentation in decomposing large RNA structures into distinct domains.  (+info)

Riboswitch function: flipping the switch or tuning the dimmer? (2/179)

Riboswitches are structured mRNA elements involved in gene regulation that respond to the intracellular concentration of specific small molecules. Binding of their cognate ligand is thought to elicit a global conformational change of the riboswitch, in addition to modulating the fine structure of the binding site. X-ray crystallography has produced detailed descriptions of the three-dimensional structures of the ligand-bound conformations of several riboswitches. We have employed small-angle X-ray scattering (SAXS) to generate low-resolution reconstructions of the ligand-free states of the ligand-binding domains of riboswitches that respond to thiamine pyrophosphate (TPP), and cyclic diguanylate (c-di-GMP), a bacterial second messenger. Comparison of the SAXS reconstructions with the crystal structures of these two riboswitches demonstrates that the RNAs undergo dramatic ligand-induced global conformational changes. However, this is not an universal feature of riboswitches. SAXS analysis of the solution behavior of several other riboswitch ligand-binding domains demonstrates a broad spectrum of conformational switching behaviors, ranging from the unambiguous switching of the TPP and c-di-GMP riboswitches to complete lack of switching for the flavin mononucleotide (FMN) riboswitch. Moreover, the switching behavior varies between examples of the same riboswitch from different organisms. The range of observed behaviors suggests that in response to the evolutionary need for precise genetic regulation, riboswitches may be tuned to function more as dimmers or rheostats than binary on/off switches.  (+info)

Experimental discovery of small RNAs in Staphylococcus aureus reveals a riboregulator of central metabolism. (3/179)

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The glmS ribozyme: use of a small molecule coenzyme by a gene-regulatory RNA. (4/179)

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Characterization of a novel riboswitch-regulated lysine transporter in Aggregatibacter actinomycetemcomitans. (5/179)

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Premature terminator analysis sheds light on a hidden world of bacterial transcriptional attenuation. (6/179)

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Synthetic riboswitches that induce gene expression in diverse bacterial species. (7/179)

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Riboswitches: structures and mechanisms. (8/179)

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