Computational Analysis of siRNA Recognition by the Ago2 PAZ Domain and Identification of the Determinants of RNA-Induced Gene Silencing

Kandeel, Mahmoud; Kitade, Yukio

doi:10.1371/journal.pone.0057140

Cited by 40 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[15][16][17] Understanding the gene's composition and subsequent analysis of codon usage is indispensable in understanding virus replication and evolution and targeting the unique aspects of virus biology. 18,19) For the 20 amino acids, 61 genetic codes are used.…”

mentioning

confidence: 99%

Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases

Kandeel

Altaher

2017

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Middle East respiratory syndrome coronavirus (MERS CoV) is a recently evolved fatal respiratory disease that poses a concern for a global epidemic. MERS CoV encodes 2 proteases, 3C-like protease (3CLpro) and papain-like protease (PLpro). These proteases share in processing MERS CoV polyproteins at different sites to yield 16 nonstructural proteins. In this work, we provide evidence that MERS CoV 3CLpro and PLpro are subject to different genetic and evolutionary influences that shape the protein sequence, codon usage pattern, and codon usage bias. Compositional bias is present in both proteins due to a preference for AT nucleotides. Thymidine (T) was highly preferred at the third position of codons, preferred and overrepresented codons in PLpro, but was replaced by guanosine (G) in 3CLpro. Compositional constraints were important in PLpro but not in 3CLpro. Directed mutation pressure seems to have a strong influence on 3CLpro codon usage, which is more than 30-fold higher than that in PLpro. Translational selection was evident with PLpro but not with 3CLpro. Both proteins are less immunogenic by showing low CpG frequencies. Correspondence analysis reveals the presence of 3 genetic clusters based on codon usage in PLpro and 3CLpro. Every protein had one common cluster and 2 different clusters. As revealed by correspondence analysis, the number of influences on codon usage are restricted in MERS CoV 3CLpro. In contrast, PLpro is controlled by a broader range of compositional, mutational, and other influences. This may be due to the multifunctional protease, deubiquitination, and innate immunity suppressing profiles of PLpro.

show abstract

mentioning

confidence: 99%

Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases

Kandeel

Altaher

2017

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…Annotations and analysis of sequences is a gold standard in the finding of new functions, drug targets and analysis of recently emerged infectious diseases [10][11][12][13][14][15]. To identify the distinguishing feature of the new MERS-CoV, the full genome sequence of MERS-CoV as well as the sequence of S protein was retrieved, compared to other CoV full genome sequences and analyzed by bioinformatics tools.…”

Section: Resultsmentioning

confidence: 99%

Bioinformatics analysis of the recent MERS-CoV with special reference to the virus-encoded Spike protein

Kandeel¹

2015

Mol Enzyme Drug Targets

Self Cite

View full text Add to dashboard Cite

Coronaviruses (CoVs) are characterized by high recombination frequencies, resulting in sudden outbreak of newly evolved viruses with different pathogenicity, tissue tropism and high genome sequence variability. Recently, an outbreak of CoVs was evolved in the Arabian Pennsylvania, which is known as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Full genome sequence analysis of MERS-CoV isolates and its comparison with other CoV full genome sequences revealed a low to medium sequence identity. Furthermore, it showed more sequence identity and phylogenetic relations with batderived CoVs and lower values with animal-derived CoVs, indicating low possibility of zoonotic origin and possible incrimination of bats in the spread of MERS-CoV. The higher neighbor homology was evident with BetaCoV and their associated SARS-CoV. The spike protein, which is a highly variable part of CoV genome and responsible for difference in tissue tropism and virus entry to the cell, showed more or less similar profile of the whole genome analysis. Furthermore, the highest identity was with those in bats with Asian origin of CoV and there was lower homology with isolates from other continents. With low human-to-human transmission and low homology with CoV of animal origin, bats are thought to be the source of MERS-CoV, especially those bearing the Asian isolates of CoV.

show abstract

“…75 cleaved product is released, the PAZ domains returns to its original position at the 3 0 end. 76 The phosphodiester backbone of the target mRNA is subsequently broken down by divalent ions (Mg 2+ ). 33 RNAi ability of siRNA can be utilized to target the cellular pathways of cancer cells that are responsible for cancer growth or metastasis.…”

Section: Chitosan-based Nanoparticlesmentioning

confidence: 99%

Nanoparticulate RNA delivery systems in cancer

et al. 2020

View full text Add to dashboard Cite

Background: Drug delivery system is a common practice in cancer treatment. RNA interference-mediated post-transcriptional gene silencing holds promise as an approach to knockdown in the expression of target genes responsible for cancer cell growth and metastasis. RNA interference (RNAi) can be achieved by delivering small interfering RNA (siRNA) and short hairpin RNA (shRNA) to target cells. Since neither interfering RNAs can be delivered in naked form due to poor stability, an efficient delivery system is required that protects, guides, and delivers the siRNA and shRNA to target cells as part of cancer therapy (chemotherapy). Recent findings: In this review, a discussion is presented about the different types of drug delivery system used to deliver siRNA and shRNA, together with an overview of the potential benefits associated with this sophisticated biomolecular therapy. Improved understanding of the different approaches used in nanoparticle (NP) fabrication, along with an enhanced appreciation of the biochemical properties of siRNA/ shRNA, will assist in developing improved drug delivery strategies in basic and clinical research. Conclusion: These novel delivery techniques are able to solve the problems that form an inevitable part of delivering genes in more efficient manner and as part of more effective treatment protocols. The present review concludes that the nanoparticulate RNA delivery system has great possibility for cancer treatment along with several other proposed methods. Several NPs or nanocarriers are already in use, but the methods proposed here could fulfill the missing gap in cancer research. It is the future technology, which unravels the mystery of resolving genomic diseases that is, especially genomic instability and its signaling cascades.

show abstract

Computational Analysis of siRNA Recognition by the Ago2 PAZ Domain and Identification of the Determinants of RNA-Induced Gene Silencing

Cited by 40 publications

References 36 publications

Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases

Synonymous and Biased Codon Usage by MERS CoV Papain-Like and 3CL-Proteases

Bioinformatics analysis of the recent MERS-CoV with special reference to the virus-encoded Spike protein

Nanoparticulate RNA delivery systems in cancer

Contact Info

Product

Resources

About