Characterization of the Role of Hexamer AGUAAA and Poly(A) Tail in Coronavirus Polyadenylation

Peng, Yu; Lin, Ching Houng; Lin, Chao; Lo, Chen‐Yu; Tsai, Tsung-Yu; Wu, Hung-Yi

doi:10.1371/journal.pone.0165077

Cited by 20 publications

(21 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in accordance with the results obtained by (Hassan et al, 2020). (Peng et al, 2016), of which only four sequences Wuhan Reference, Hyderabad (Telangana), South 24 Parganas, and Howrah (West Bengal) (viz., NC_045512, EPI_ISL_431102, 437537, 437537) had a poly-A tail after 57 bases. The remaining sequences were terminated between 53-58 bases downstream, without a poly-A tail.…”

Section: Shannon Entropysupporting

confidence: 92%

“…The first available SARS-CoV-2 isolate from Kerala (EPI_ISL_413522) is devoid of polymight signify a different origin of the Indian isolate when compared to the Chinese isolate, or it may denote an indel (Chatterjee, 2020) as it is well known that the poly-A tail plays a significant role during infection. Truncation of the poly-A tail in Kerala isolate is probably due to sequencing errors or may be due to tail length regulation in coronavirus as the length is not static (Peng et al, 2016). However, it cannot signify a Chatterjee (2020).…”

Section: Shannon Entropymentioning

confidence: 99%

See 1 more Smart Citation

Phylogeographic analysis of SARS-CoV-2 variations from Indian isolates

Joshipura¹,

Balaji²

2020

Preprint

View full text Add to dashboard Cite

The aggressive multiplication of coronavirus in the Indian population is probably due to the faster mutation rate. At the time of commencement of this work, India was not present in the list of Top 10 worst-affected countries. However, upon completion of this manuscript, India is ranked No. 3 and during publication of this manuscript it may even elevate to the top two positions due to the pandemic. In this study, SARS-CoV-2 isolates of Indian origin were compared with the Wuhan reference sequence. Phylogenomic, proteomic, and phylogeographic analyses were performed. The genome comparisons indicated that majority of the sequence variations are associated with protein-coding regions, especially Orf1a and spike glycoproteins, while Orf7a had consistent variations, whereas Orfs 6a, 8 and 10 had negligible variations. The terminals of the genomes compared had high sequence entropy. However, the polyadenylation signal was invariant in the analysed dataset. The codon usage frequency indicated that UGU (code for cysteine) is the most frequent codon, while the least frequent was GCG (code for alanine). The amino acid frequency showed that the most abundant was leucine (12.5%), and the least was histidine (2.45%). The phylogeographical patterns were mapped for all the representative states of India, and were supplemented with few representative countries. The unique differences in the sequence of the Kerala isolate (EPI_ISL_413522) were resolved to be sequence errors rather than mutations. Based on the phylogeographic analysis, the high probability of mutations likely to be of Indian origin is attributed to the Gujarat cluster.

show abstract

Section: Shannon Entropysupporting

confidence: 92%

Section: Shannon Entropymentioning

confidence: 99%

Phylogeographic analysis of SARS-CoV-2 variations from Indian isolates

Joshipura¹,

Balaji²

2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Studies from influenza virus revealed that a short polyU sequence within a unique RNA stem−loop mediates a stuttering mechanism used to polyadenylate the positive-sense RNA (45). In contrast, Peng et al (46) implicate that CoVs utilize a noncanonical cytoplasmic polyadenylation site to synthesize the positive-sense polyA tail. They identified a conserved viral sequence on the positive-sense RNA that could be bound by host proteins, including cytoplasmic polyadenylation element binding protein 1 (CPEB1) (47), a protein that mediates polyadenylation.…”

Section: Discussionmentioning

confidence: 99%

Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors

Hackbart

Deng

Baker

2020

Proc. Natl. Acad. Sci. U.S.A.

263

265

View full text Add to dashboard Cite

Coronaviruses (CoVs) are positive-sense RNA viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease designated EndoU that facilitates evasion of host pattern recognition receptor MDA5, but the target of EndoU activity was not known. Here, we report that EndoU cleaves the 5′-polyuridines from negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNA synthesis. Using a virus containing an EndoU catalytic-inactive mutation, we detected a higher abundance of PUN RNA in the cytoplasm compared to wildtype−infected cells. Furthermore, we found that transfecting PUN RNA into cells stimulates a robust, MDA5-dependent interferon response, and that removal of the polyuridine extension on the RNA dampens the response. Overall, the results of this study reveal the PUN RNA to be a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). We also establish a mechanism for EndoU activity to cleave and limit the accumulation of this PAMP. Since EndoU activity is highly conserved in all CoVs, inhibiting this activity may serve as an approach for therapeutic interventions against existing and emerging CoV infections.C oronaviruses (CoVs) are positive-sense RNA viruses that replicate in the cytoplasm of infected cells. The positivesense virion RNA is translated to generate the viral replication machinery, which then replicates the positive-sense RNA into negative-sense, genomic RNA and subgenomic RNAs (sgRNAs). The negative-sense RNAs then function as templates for synthesis of positive-sense genomic RNA and sgRNA (1, 2). This replication strategy can generate long double-stranded RNA (dsRNA) intermediates (3), that may act as pathogen-associated molecular patterns (PAMPs) recognized by cytoplasmic pattern recognition receptors (PRRs) (4, 5). The specific PRR that recognizes CoV RNA is MDA5, which can activate the type I interferon (IFN) response in macrophages (6). Other host dsRNA PRRs, such as PKR and OAS, are also activated and operate to limit CoV replication (7-11). CoVs encode multiple proteins that antagonize these innate immune responses, particularly the activation of the IFN response (9, 12-16), ultimately leading to a dysregulated immune response and increased immunopathogenesis (17,18). Understanding the mechanisms used by CoVs to delay IFN signaling may provide opportunities for the development of antivirals and live-attenuated vaccines to limit CoV infections.Here, we investigate the mechanism used by one CoV IFN antagonist, the nonstructural protein 15 (nsp15), which is an endoribonuclease designated EndoU. EndoU is highly conserved in all known CoVs (19,20). EndoU is similar to the cellular endoribonuclease XendoU, as revealed by bioinformatic analysis of the amino acid sequence (21). X-ray structures of EndoU revealed conserved endoribonuclease folds with catalytic histidine residues required for endoribonuclease activity (22)(23)(24)(25)(26). Purified EndoU was shown to cleave single-str...

show abstract

“…Various deletions and insertions in the 3= UTR as well as complete deletion of the poly(A) tail may not kill alphaviruses (457)(458)(459), flaviviruses (460)(461)(462), coronaviruses (463)(464)(465), and various plant viruses (466)(467)(468)(469). The repair of the damaged genomes may again involve different mechanisms, including RNA recombination, the use of the viral RdRP-or host-dependent polyadenylation activities, and perhaps some others.…”

Section: Some Additional Lessons From Other Rna Viruses Positive-stramentioning

confidence: 99%

Emergency Services of Viral RNAs: Repair and Remodeling

Agol

Gmyl

2018

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.

show abstract

Characterization of the Role of Hexamer AGUAAA and Poly(A) Tail in Coronavirus Polyadenylation

Cited by 20 publications

References 63 publications

Phylogeographic analysis of SARS-CoV-2 variations from Indian isolates

Phylogeographic analysis of SARS-CoV-2 variations from Indian isolates

Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors

Emergency Services of Viral RNAs: Repair and Remodeling

Contact Info

Product

Resources

About