scholarly journals Functional RNA Elements in the Dengue Virus Genome

Viruses ◽  
2011 ◽  
Vol 3 (9) ◽  
pp. 1739-1756 ◽  
Author(s):  
Leopoldo G. Gebhard ◽  
Claudia V. Filomatori ◽  
Andrea V. Gamarnik
2005 ◽  
Vol 79 (11) ◽  
pp. 6631-6643 ◽  
Author(s):  
Diego E. Alvarez ◽  
María F. Lodeiro ◽  
Silvio J. Ludueña ◽  
Lía I. Pietrasanta ◽  
Andrea V. Gamarnik

ABSTRACT Secondary and tertiary RNA structures present in viral RNA genomes play essential regulatory roles during translation, RNA replication, and assembly of new viral particles. In the case of flaviviruses, RNA-RNA interactions between the 5′ and 3′ ends of the genome have been proposed to be required for RNA replication. We found that two RNA elements present at the ends of the dengue virus genome interact in vitro with high affinity. Visualization of individual molecules by atomic force microscopy reveled that physical interaction between these RNA elements results in cyclization of the viral RNA. Using RNA binding assays, we found that the putative cyclization sequences, known as 5′ and 3′ CS, present in all mosquito-borne flaviviruses, were necessary but not sufficient for RNA-RNA interaction. Additional sequences present at the 5′ and 3′ untranslated regions of the viral RNA were also required for RNA-RNA complex formation. We named these sequences 5′ and 3′ UAR (upstream AUG region). In order to investigate the functional role of 5′-3′ UAR complementarity, these sequences were mutated either separately, to destroy base pairing, or simultaneously, to restore complementarity in the context of full-length dengue virus RNA. Nonviable viruses were recovered after transfection of dengue virus RNA carrying mutations either at the 5′ or 3′ UAR, while the RNA containing the compensatory mutations was able to replicate. Since sequence complementarity between the ends of the genome is required for dengue virus viability, we propose that cyclization of the RNA is a required conformation for viral replication.


2020 ◽  
Vol 27 (9) ◽  
pp. 870-870
Author(s):  
Marc Bühler ◽  
Alex Charles Tuck

2020 ◽  
Vol 118 (3) ◽  
pp. 70a
Author(s):  
Alex Plumridge ◽  
Lois Pollack

Cell Reports ◽  
2020 ◽  
Vol 32 (1) ◽  
pp. 107859 ◽  
Author(s):  
Berati Cerikan ◽  
Sarah Goellner ◽  
Christopher John Neufeldt ◽  
Uta Haselmann ◽  
Klaas Mulder ◽  
...  

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Laura A. Byk ◽  
Néstor G. Iglesias ◽  
Federico A. De Maio ◽  
Leopoldo G. Gebhard ◽  
Mario Rossi ◽  
...  

ABSTRACTThe process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process.IMPORTANCEDengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade regarding molecular aspects of the fusion step, but little is known about the events that follow this process, which leads to viral RNA release from the nucleocapsid. Here, we investigated the fate of nucleocapsid components (capsid protein and viral genome) during the infection process and found that capsid is degraded by the ubiquitin-proteasome system. However, in contrast to that observed for other RNA and DNA viruses, dengue virus capsid degradation was not responsible for genome uncoating. Interestingly, we found that dengue virus genome release requires a nondegradative ubiquitination step. These results provide the first insights into dengue virus uncoating and present new opportunities for antiviral intervention.


2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Meiranty C. Pangerapan ◽  
Beivy J. Kolondam

Abstract: Dengue virus is a single-stranded RNA virus that belongs to Flaviviridae family. This virus causes dengue fever which is transmitted by Aedes aegypti dan Aedes albopictus. There are four serotypes of dengue virus; all of them can cause dengue fever. Understanding the genomics of dengue virus is important for research and diagnostics. The genome of dengue virus is 11 kilo-base long. It consists of 5’-untranslated region (5’-UTR), three structural genes (coding capsid protein, pre-membrane/membrane, and envelope), seven non-structural genes (coding NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 proteins) and 3’-UTR. Non-structural genes are encoding proteins of viral RNA replication, interferon response, viral assembly and secretion, endoplasmic reticulum membrane invagination induction, immune-mediator induction, and RNA 5’-caping.Keywords: dengue virus, genome, structural genes, non-structural genes, untranslated region.Abstrak: Virus dengue merupakan virus RNA beruntai tunggal yang termasuk dalam famili Flaviviridae. Virus ini adalah penyebab penyakit demam berdarah dengue yang ditransmisikan melalui nyamuk Aedes aegypti dan Aedes albopictus. Ada empat serotipe virus dengue yang telah dikenal secara luas yang ada semuanya dapat menimbulkan penyakit demam berdarah. Pemahaman tentang genomik virus dengue sangat penting untuk pengembangan penelitian dan juga untuk keperluan diagnostik. Genom virus dengue memiliki panjang 11 kilo basa. Genomnya tersusun atas 5’-untranslated region (5’-UTR), tiga gen struktural (mengodekan protein kapsid, premembran/membran dan amplop), tujuh gen non-struktural (mengodekan protein NS1, NS2A, NS2B, NS3, NS4A, NS4B dan NS5) dan 3’-UTR. Gen-gen non-struktural mengodekan protein untuk replikasi RNA virus, respon interferon, perakitan, sekresi partikel virus, menginduksi invaginasi membran retikulum endoplasma, induksi imunomediator dan penambahan tudung pada ujung 5’ RNA.Kata kunci: virus dengue, genom, gen struktural, gen non-struktural, untranslated region


2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Masahiro Onoguchi ◽  
Chao Zeng ◽  
Ayako Matsumaru ◽  
Michiaki Hamada

Abstract Recent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA-binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.


Fractals ◽  
2020 ◽  
Vol 28 (07) ◽  
pp. 2050129
Author(s):  
HAMIDREZA NAMAZI

Coronavirus disease (COVID-19) is a pandemic disease that has affected almost all around the world. The most crucial step in the treatment of patients with COVID-19 is to investigate about the coronavirus itself. In this research, for the first time, we analyze the complex structure of the coronavirus genome and compare it with the other two dangerous viruses, namely, dengue and HIV. For this purpose, we employ fractal theory, sample entropy, and approximate entropy to analyze the genome walk of coronavirus, dengue virus, and HIV. Based on the obtained results, the genome walk of coronavirus has greater complexity than the other two deadly viruses. The result of statistical analysis also showed the significant difference between the complexity of genome walks in case of all complexity measures. The result of this analysis opens new doors to scientists to consider the complexity of a virus genome as an index to investigate its danger for human life.


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