scholarly journals New opportunities for designing effective small interfering RNAs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
James J. Valdés ◽  
Andrew D. Miller

Abstract Small interfering RNAs (siRNAs) that silence genes of infectious diseases are potentially potent drugs. A continuing obstacle for siRNA-based drugs is how to improve their efficacy for adequate dosage. To overcome this obstacle, the interactions of antiviral siRNAs, tested in vivo, were computationally examined within the RNA-induced silencing complex (RISC). Thermodynamics data show that a persistent RISC cofactor is significantly more exothermic for effective antiviral siRNAs than their ineffective counterparts. Detailed inspection of viral RNA secondary structures reveals that effective antiviral siRNAs target hairpin or pseudoknot loops. These structures are critical for initial RISC interactions since they partially lack intramolecular complementary base pairing. Importing two temporary RISC cofactors from magnesium-rich hairpins and/or pseudoknots then kickstarts full RNA hybridization and hydrolysis. Current siRNA design guidelines are based on RNA primary sequence data. Herein, the thermodynamics of RISC cofactors and targeting magnesium-rich RNA secondary structures provide additional guidelines for improving siRNA design.

2020 ◽  
Vol 8 (4) ◽  
pp. 369-381
Author(s):  
Jianyu Zhou ◽  
Pan Li ◽  
Wanwen Zeng ◽  
Wenxiu Ma ◽  
Zhipeng Lu ◽  
...  

2013 ◽  
Vol 88 (2) ◽  
pp. 219-229
Author(s):  
A. Chaudhary ◽  
N. Singh ◽  
H.S. Singh

AbstractNematodes of the family Thelastomatidae are parasitic in the alimentary tract of many arthropods, including Periplaneta americana L. In Meerut, Uttar Pradesh, India, two nematode species, namely Hammerschmidtiella indicus and Thelastoma icemi, belonging to this family have been reported. In the present study, the molecular phylogeny of these two nematode species was derived using small subunit (18S) sequence and secondary-structure analyses. The small subunit sequence analyses were carried out to explore the validation and systematics of these species. Phylogenetic analyses were performed for primary sequence data as well as using neighbour-joining and maximum-parsimony approaches. In contrast, the inferred secondary structures for the two species, using free-energy modelling, showed structural identities. As well as this, motif sequences were also found to be a promising tool for nematode species identification. The study provides molecular characterization based on primary sequence data of the 18S ribosomal DNA region of the nematodes along with secondary-structure data and motif sequences for inferences at higher taxonomic levels.


1991 ◽  
Vol 275 (2) ◽  
pp. 529-534 ◽  
Author(s):  
I B Wilson ◽  
Y Gavel ◽  
G von Heijne

To study the sequence requirements for addition of O-linked N-acetylgalactosamine to proteins, amino acid distributions around 174 O-glycosylation sites were compared with distributions around non-glycosylated sites. In comparison with non-glycosylated serine and threonine residues, the most prominent feature in the vicinity of O-glycosylated sites is a significantly increased frequency of proline residues, especially at positions -1 and +3 relative to the glycosylated residues. Alanine, serine and threonine are also significantly increased. The high serine and threonine content of O-glycosylated regions is due to the presence of clusters of several closely spaced glycosylated hydroxy amino acids in many O-glycosylated proteins. Such clusters can be predicted from the primary sequence in some cases, but there is no apparent possibility of predicting isolated O-glycosylation sites from primary sequence data.


2002 ◽  
Vol 79 (1) ◽  
pp. 1-9 ◽  
Author(s):  
GUGS LUSHAI ◽  
HUGH D. LOXDALE

Emperical evidence for intraclonal genetic variation is described here for clonal systems using a variety of molecular techniques and implicating a diversity of mechanisms. However, clonal systems are still generally perceived as having strict genetic fidelity. As concepts of genetic variability move from primary sequence data to include epigenetic and structural influences on genetic expression, the ability to detect changes in the genome at short intervals allows precedence to be given to inherent biological variation that is often analytically ignored. Therefore, the advent of powerful molecular techniques, like genome mapping, mean that our concepts of genetic fidelity within eukaryotic clones and the whole philosophy of the ‘clone’ needs to be re-evaluated and re-defined to replace old unproven dogma in this aspect of science.


2020 ◽  
Vol 36 (11) ◽  
pp. 3578-3579
Author(s):  
Michela Quadrini ◽  
Luca Tesei ◽  
Emanuela Merelli

Abstract Summary Current methods for comparing RNA secondary structures are based on tree representations and exploit edit distance or alignment algorithms. Most of them can only process structures without pseudoknots. To overcome this limitation, we introduce ASPRAlign, a Java tool that aligns particular algebraic tree representations of RNA. These trees neglect the primary sequence and can handle structures with arbitrary pseudoknots. A measure of comparison, called ASPRA distance, is computed with a worst-case time complexity of O(n2) where n is the number of nucleotides of the longer structure. Availability and implementation ASPRAlign is implemented in Java and source code is released under the GNU GPLv3 license. Code and documentation are freely available at https://github.com/bdslab/aspralign. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.


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