scholarly journals Mutation in position of 32 (G>U) of S2M differentiate human SARS-CoV2 from Bat Coronavirus

2020 ◽  
Author(s):  
Majid Vahed ◽  
Mohammad Vahed ◽  
Aaron Sweeney ◽  
Farshad H Shirazi ◽  
Mehdi Mirsaeidi
Keyword(s):  
Genomic Sequence ◽  
Therapeutic Agents ◽  
Regulatory Rna ◽  
Host Defenses ◽  
Rna Structures ◽  
Host Proteins ◽  
Tertiary Structures ◽  
Stem Loop ◽  
The Impact ◽  
Bat Coronavirus

ABSTRACTThe new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic pathogen that has rapidly mutated and become transmissible to humans. There is little existing data on the mutations in SARS-CoV-2 and the impact of these polymorphisms on its transmission and viral load. In this study, the SARS-CoV-2 genomic sequence was analyzed to identify variants within the 3’UTR region of its cis-regulatory RNA elements. A 43-nucleotide genetic element with a highly conserved stem-loop II-like motif (S2M), was discovered. The research revealed 32 G>U and 16 G>U/A mutations located within the S2M sequence in human SARS-CoV-2 models. These polymorphisms appear to make the S2M secondary and tertiary structures in human SARS-CoV-2 models less stable when compared to the S2M structures of bat/pangolin models. This grants the RNA structures more flexibility, which could be one of its escape mechanisms from host defenses or facilitate its entry into host proteins and enzymes. While this S2M sequence may not be omnipresent across all human SARS-CoV-2 models, when present, its sequence is always highly conserved. It may be used as a potential target for the development of vaccines and therapeutic agents.

scholarly journals Analysis of Rapidly Emerging Variants in Structured Regions of the SARS-CoV-2 Genome

2020 ◽  
Author(s):  
Sean P. Ryder ◽  
Brittany R. Morgan ◽  
Francesca Massi
Keyword(s):  
High Throughput Sequencing ◽  
Hypervariable Region ◽  
Regulatory Elements ◽  
Regulatory Rna ◽  
Rna Structures ◽  
Stem Loop ◽  
Functional Relevance ◽  
The Stability ◽  
Genome Heterogeneity ◽  
A Minor

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around the globe. They also provide a unique opportunity to observe virus evolution in real time. Here, we evaluate two cohorts of SARS-CoV-2 genomic sequences to identify rapidly emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, twenty variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5’UTR, including a set of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-stable molecular switch in the 3’UTR. Finally, five variants destabilize structured elements within the 3’UTR hypervariable region, including the S2M stem loop, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. This analysis has implications for the development of therapeutics that target viral cis-regulatory RNA structures or sequences, as rapidly emerging variations in these regions could lead to drug resistance.

scholarly journals 1H, 13C and 15N assignment of stem-loop SL1 from the 5'-UTR of SARS-CoV-2

2021 ◽  
Author(s):  
Christian Richter ◽  
Katharina F. Hohmann ◽  
Sabrina Toews ◽  
Daniel Mathieu ◽  
Nadide Altincekic ◽  
...  
Keyword(s):  
Life Cycle ◽  
Chemical Shift ◽  
Base Pair ◽  
Chemical Shift Assignment ◽  
Potential Functions ◽  
Regulatory Rna ◽  
Structural Element ◽  
Stem Loop ◽  
Internal Loop ◽  
Shift Assignment

AbstractThe stem-loop (SL1) is the 5'-terminal structural element within the single-stranded SARS-CoV-2 RNA genome. It is formed by nucleotides 7–33 and consists of two short helical segments interrupted by an asymmetric internal loop. This architecture is conserved among Betacoronaviruses. SL1 is present in genomic SARS-CoV-2 RNA as well as in all subgenomic mRNA species produced by the virus during replication, thus representing a ubiquitous cis-regulatory RNA with potential functions at all stages of the viral life cycle. We present here the 1H, 13C and 15N chemical shift assignment of the 29 nucleotides-RNA construct 5_SL1, which denotes the native 27mer SL1 stabilized by an additional terminal G-C base-pair.

scholarly journals Interactions between highly conserved U2 small nuclear RNA structures and Prp5p, Prp9p, Prp11p, and Prp21p proteins are required to ensure integrity of the U2 small nuclear ribonucleoprotein in Saccharomyces cerevisiae.

1994 ◽  
Vol 14 (9) ◽  
pp. 6337-6349 ◽  
Author(s):  
S E Wells ◽  
M Ares
Keyword(s):  
Synthetic Lethality ◽  
Small Nuclear Rna ◽  
Rna Structures ◽  
Stem Loop ◽  
U2 Snrna ◽  
Small Nuclear Ribonucleoprotein ◽  
U2 Snrnp ◽  
Nuclear Rna ◽  
Nuclear Ribonucleoprotein

Binding of U2 small nuclear ribonucleoprotein (snRNP) to the pre-mRNA is an early and important step in spliceosome assembly. We searched for evidence of cooperative function between yeast U2 small nuclear RNA (snRNA) and several genetically identified splicing (Prp) proteins required for the first chemical step of splicing, using the phenotype of synthetic lethality. We constructed yeast strains with pairwise combinations of 28 different U2 alleles with 10 prp mutations and found lethal double-mutant combinations with prp5, -9, -11, and -21 but not with prp3, -4, -8, or -19. Many U2 mutations in highly conserved or invariant RNA structures show no phenotype in a wild-type PRP background but render mutant prp strains inviable, suggesting that the conserved but dispensable U2 elements are essential for efficient cooperative function with specific Prp proteins. Mutant U2 snRNA fails to accumulate in synthetic lethal strains, demonstrating that interaction between U2 RNA and these four Prp proteins contributes to U2 snRNP assembly or stability. Three of the proteins (Prp9p, Prp11p, and Prp21p) are associated with each other and pre-mRNA in U2-dependent splicing complexes in vitro and bind specifically to synthetic U2 snRNA added to crude splicing extracts depleted of endogenous U2 snRNPs. Taken together, the results suggest that Prp9p, -11p, and -21p are U2 snRNP proteins that interact with a structured region including U2 stem loop IIa and mediate the association of the U2 snRNP with pre-mRNA.

scholarly journals New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes

2011 ◽  
Vol 21 (11) ◽  
pp. 1929-1943 ◽  
Author(s):  
B. J. Parker ◽  
I. Moltke ◽  
A. Roth ◽  
S. Washietl ◽  
J. Wen ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Regulatory Rna ◽  
Rna Structures

The impact of translational research on the development of therapeutic agents for multiple sclerosis

2021 ◽  
pp. 203-242
Author(s):  
Stanley L. Cohan ◽  
Elisabeth B. Lucassen ◽  
Kyle E. Smoot ◽  
Kiren Kresa-Reahl ◽  
Meghan Romba ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Translational Research ◽  
Therapeutic Agents ◽  
The Impact

scholarly journals An NMR-based approach reveals the core structure of the functional domain of SINEUP lncRNAs

2020 ◽  
Vol 48 (16) ◽  
pp. 9346-9360
Author(s):  
Takako Ohyama ◽  
Hazuki Takahashi ◽  
Harshita Sharma ◽  
Toshio Yamazaki ◽  
Stefano Gustincich ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Computational Prediction ◽  
Functional Domain ◽  
Rna Structures ◽  
Tertiary Structures ◽  
Functional Roles ◽  
The Core ◽  
Non Coding Rnas ◽  
Dynamic Domain

Abstract Long non-coding RNAs (lncRNAs) are attracting widespread attention for their emerging regulatory, transcriptional, epigenetic, structural and various other functions. Comprehensive transcriptome analysis has revealed that retrotransposon elements (REs) are transcribed and enriched in lncRNA sequences. However, the functions of lncRNAs and the molecular roles of the embedded REs are largely unknown. The secondary and tertiary structures of lncRNAs and their embedded REs are likely to have essential functional roles, but experimental determination and reliable computational prediction of large RNA structures have been extremely challenging. We report here the nuclear magnetic resonance (NMR)-based secondary structure determination of the 167-nt inverted short interspersed nuclear element (SINE) B2, which is embedded in antisense Uchl1 lncRNA and upregulates the translation of sense Uchl1 mRNAs. By using NMR ‘fingerprints’ as a sensitive probe in the domain survey, we successfully divided the full-length inverted SINE B2 into minimal units made of two discrete structured domains and one dynamic domain without altering their original structures after careful boundary adjustments. This approach allowed us to identify a structured domain in nucleotides 31–119 of the inverted SINE B2. This approach will be applicable to determining the structures of other regulatory lncRNAs.

Identification of microRNAs from rice

2005 ◽  
Vol 32 (10) ◽  
pp. 963 ◽  
Author(s):  
Yu-Zhu Lu ◽  
Da-Wei Yan ◽  
Ying-Tang Lu
Keyword(s):  
Genomic Sequence ◽  
Oryza Sativa L ◽  
Gene Families ◽  
Loop Structure ◽  
Food Crop ◽  
Important Food ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Unknown Protein ◽  
Computational Analyses

MicroRNAs (miRNAs) are important regulators in the development of plants and animals. Several hundred have been identified from animals, and about a dozen have been cloned from plants, mainly Arabidopsis thaliana (L.) Heynh. We have identified nine miRNAs in Oryza sativa L., an important food crop that has been sequenced in recent years. The nine miRNAs include miRNA171 and miRNA167, which were also identified in Arabidopsis. These had the typical properties of miRNAs, including short length, an ability to form a stem–loop structure with a flanking genomic sequence and they could be identified by northern blot analyses. In addition, m-fold program and computational analyses indicted that the potential targets of six of the nine miRNAs are four known gene families and two unknown protein families, which comprise 16 unique genes.

scholarly journals Structure of interferon-stimulated gene product 15 (ISG15) from the bat species Myotis davidii and the impact of interdomain ISG15 interactions on viral protein engagement

2019 ◽  
Vol 75 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Caroline Langley ◽  
Octavia Goodwin ◽  
John V. Dzimianski ◽  
Courtney M. Daczkowski ◽  
Scott D. Pegan
Keyword(s):  
Gene Product ◽  
Species Differences ◽  
Viral Proteins ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Host Proteins ◽  
Post Translational Modifications ◽  
Interferon Responses ◽  
The Impact

Bats have long been observed to be the hosts and the origin of numerous human diseases. Bats, like all mammals, rely on a number of innate immune mechanisms to combat invading pathogens, including the interferon type I, II and III responses. Ubiquitin-like interferon-stimulated gene product 15 (ISG15) is a key modulator of these interferon responses. Within these pathways, ISG15 can serve to stabilize host proteins modulating innate immune responses and act as a cytokine. Post-translational modifications of viral proteins introduced by ISG15 have also been observed to directly affect the function of numerous viral proteins. Unlike ubiquitin, which is virtually identical across all animals, comparison of ISG15s across species reveals that they are relatively divergent, with sequence identity dropping to as low as ∼58% among mammals. In addition to serving as an obstacle to the zoonotic transmission of influenza, these ISG15 species–species differences have also long been shown to have an impact on the function of viral deISGylases. Recently, the structure of the first nonhuman ISG15, originating from mouse, suggested that the structures of human ISG15 may not be reflective of other species. Here, the structure of ISG15 from the bat species Myotis davidii solved to 1.37 Å resolution is reported. Comparison of this ISG15 structure with those from human and mouse not only underscores the structural impact of ISG15 species–species differences, but also highlights a conserved hydrophobic motif formed between the two domains of ISG15. Using the papain-like deISGylase from Severe acute respiratory syndrome coronavirus as a probe, the biochemical importance of this motif in ISG15–protein engagements was illuminated.

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