RNA folding pathway functional intermediates: their prediction and analysis 1 1Edited by I. Tinoco

Shapiro, Bruce A.; Bengali, David; Kasprzak, Wojciech K.; Wu, Jiemin

doi:10.1006/jmbi.2001.4931

Cited by 61 publications

(58 citation statements)

References 32 publications

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“…The MPGAfold algorithm (47,50,56,57), starting from a pool of randomly generated stem-loop structures from a given RNA sequence, recombines these parent structures over multiple generations until the population of RNA molecules evolves and reaches a consensus RNA structure. Because of the stochastic nature of MPGAfold, multiple independent runs must be done to determine the overall consensus structure for the given RNA.…”

Section: The 3ј-db Forms a Stable Secondary Structure Whereas The 5јmentioning

confidence: 99%

“…In contrast, there seems to be a differential role for TL1/PK2 and TL2/PK1 in translation. The lack of functional similarity between TL1 and TL2 despite their identical sequences within two DBs could be explained by results of our analysis of RNA secondary structures, their stabilities, and frequency of occurrence computed by the massively parallel genetic algorithm (MPGAfold) (47)(48)(49)(50)(51). The results of our study, taken together, provide a new insight into the role of the cis-acting elements in the CR region in translation and replication.…”

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confidence: 99%

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Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication

Manzano

Reichert

Polo

et al. 2011

Journal of Biological Chemistry

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124

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Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5-and 3-DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3-DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by ϳ60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation. The dengue virus (DENV)3 is a mosquito-borne flavivirus (MBFV) in the Flaviviridae family that consists of over 70 members, many of which are significant human pathogens (1). The MBFV members are classified into three subgroups: DENV, yellow fever virus, and Japanese encephalitis virus (JEV) (2, 3). The four serotypes of DENV (DENV1 to -4) cause an estimated 50 million cases of infections, with ϳ10% of those leading to severe forms of the disease, dengue hemorrhagic fever and dengue shock syndrome (4 -6).The viral genome is a single-stranded RNA of positive (ϩ) polarity containing ϳ11 kilobases (10,723 nt for DENV2 New Guinea C strain, GenBank TM accession number M29095 (7)). The 3Ј-end is non-polyadenylated, and the 5Ј-end has a type I cap structure (for a review, see Ref. 8). Flanking the single long open reading frame are the 5Ј-and 3Ј-UTRs, which contain conserved cis-acting RNA secondary structure elements required for translation and replication (9 -18). The viral RNA is translated to form a polyprotein precursor, which is processed by host and viral proteases in the endoplasmic reticulum membrane. Protein processing gives rise to three structural (C, prM, and E) and seven nonstructural (NS) proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5 in that order (for reviews, see Refs. 8,19,and 20) and references therein). According to the current model for replication, assembly of the viral replicase complex occurs in a cytoplasmic membrane organelle, followed by negative (Ϫ)-strand RNA synthesis starting at the 3Ј-end of the viral genome, resulting in a double-stranded replicative form. NS3 and NS5 are multifunctional pr...

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Section: The 3ј-db Forms a Stable Secondary Structure Whereas The 5јmentioning

confidence: 99%

mentioning

confidence: 99%

Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication

Manzano

Reichert

Polo

et al. 2011

Journal of Biological Chemistry

Self Cite

124

View full text Add to dashboard Cite

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“…Users of this software tend to assume that RNA folds will undertake their most thermodynamically stable form, the structure with the minimal free energy, but unfortunately in nature, if one examines functional RNAs like tRNA and RNase P RNA, this is not always true. Correct structures are believed to usually lie within 10% of the minimum energy value predicted (Shapiro et al 2001), and therefore MFOLD and similar programs will also produce suboptimal folds to increase the likelihood of an accurate prediction. MFOLD has some common limitations in that it cannot predict interloop base pairing or pseudoknots and, like all other programs, does not show noncanonical base pairing with the exception of the G-U wobble, although noncanonical pairing energy values are calculated from the energy tables.…”

Section: Single Sequence Structure Prediction Thermodynamicsmentioning

confidence: 99%

“…A massively parallel implementation of this algorithm for several supercomputers has predicted 80%-90% of the correct base pairing in the poliovirus 59-UTR (Shapiro et al 2001). The accuracy is dependent on the initial population size.…”

Section: Genetic Algorithmmentioning

confidence: 99%

Searching for IRES

Baird¹,

Turcotte²,

Korneluk³

et al. 2006

RNA

276

270

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The cell has many ways to regulate the production of proteins. One mechanism is through the changes to the machinery of translation initiation. These alterations favor the translation of one subset of mRNAs over another. It was first shown that internal ribosome entry sites (IRESes) within viral RNA genomes allowed the production of viral proteins more efficiently than most of the host proteins. The RNA secondary structure of viral IRESes has sometimes been conserved between viral species even though the primary sequences differ. These structures are important for IRES function, but no similar structure conservation has yet to be shown in cellular IRES. With the advances in mathematical modeling and computational approaches to complex biological problems, is there a way to predict an IRES in a data set of unknown sequences? This review examines what is known about cellular IRES structures, as well as the data sets and tools available to examine this question. We find that the lengths, number of upstream AUGs, and %GC content of 59-UTRs of the human transcriptome have a similar distribution to those of published IRES-containing UTRs. Although the UTRs containing IRESes are on the average longer, almost half of all 59-UTRs are long enough to contain an IRES. Examination of the available RNA structure prediction software and RNA motif searching programs indicates that while these programs are useful tools to fine tune the empirically determined RNA secondary structure, the accuracy of de novo secondary structure prediction of large RNA molecules and subsequent identification of new IRES elements by computational approaches, is still not possible.

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“…This strategy is widely used in Monte Carlo simulations 12; 13 and in genetic algorithms for obtaining folding pathways. 14; 15 We calculate the Boltzmann transition probability ij K (or transition rate) of moving from i q to j q using Metropolis rules: 40…”

Section: Accepted M Manuscript -19 -mentioning

confidence: 99%