The identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3AB

Tang, Fenfen; Xia, Hongjie; Wang, Peipei; Yang, Jie; Zhao, Tianyong; Zhāng, Qí; Hu, Yuanyang; Zhou, Xi

doi:10.1016/j.virol.2014.07.037

Cited by 10 publications

(10 citation statements)

References 50 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, enterovirus 2C ATPase is not the only RNA remodeling protein encoded by enteroviruses. Previous studies by DeStefano and colleagues showed that poliovirus 3AB is an RNA chaperone [ 42 , 57 ]; moreover, our previous report confirmed that EV71 3AB also contains in vitro RNA chaperone activity [ 58 ]. In addition, poliovirus 3D pol has been reported to display unwindase activity that does not require ATP hydrolysis but does require an RNA chain elongation reaction [ 59 ].…”

Section: Discussionsupporting

confidence: 63%

Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone

et al. 2015

Self Cite

View full text Add to dashboard Cite

RNA helicases and chaperones are the two major classes of RNA remodeling proteins, which function to remodel RNA structures and/or RNA-protein interactions, and are required for all aspects of RNA metabolism. Although some virus-encoded RNA helicases/chaperones have been predicted or identified, their RNA remodeling activities in vitro and functions in the viral life cycle remain largely elusive. Enteroviruses are a large group of positive-stranded RNA viruses in the Picornaviridae family, which includes numerous important human pathogens. Herein, we report that the nonstructural protein 2CATPase of enterovirus 71 (EV71), which is the major causative pathogen of hand-foot-and-mouth disease and has been regarded as the most important neurotropic enterovirus after poliovirus eradication, functions not only as an RNA helicase that 3′-to-5′ unwinds RNA helices in an adenosine triphosphate (ATP)-dependent manner, but also as an RNA chaperone that destabilizes helices bidirectionally and facilitates strand annealing and complex RNA structure formation independently of ATP. We also determined that the helicase activity is based on the EV71 2CATPase middle domain, whereas the C-terminus is indispensable for its RNA chaperoning activity. By promoting RNA template recycling, 2CATPase facilitated EV71 RNA synthesis in vitro; when 2CATPase helicase activity was impaired, EV71 RNA replication and virion production were mostly abolished in cells, indicating that 2CATPase-mediated RNA remodeling plays a critical role in the enteroviral life cycle. Furthermore, the RNA helicase and chaperoning activities of 2CATPase are also conserved in coxsackie A virus 16 (CAV16), another important enterovirus. Altogether, our findings are the first to demonstrate the RNA helicase and chaperoning activities associated with enterovirus 2CATPase, and our study provides both in vitro and cellular evidence for their potential roles during viral RNA replication. These findings increase our understanding of enteroviruses and the two types of RNA remodeling activities.

show abstract

Section: Discussionsupporting

confidence: 63%

Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…DeStefano and colleagues have showed that poliovirus protein 3AB possesses properties consistent with classical RNA chaperone proteins, and was able to greatly accelerate the rate of annealing between complementary nucleic acids and destabilize short double-stranded RNA substrates (DeStefano and Titilope, 2006). Moreover, our group has also demonstrated that protein 3AB from EV71 has RNA chaperone activity (Tang et al, 2014). These findings suggest that RNA chaperone activity is a general function of nonstructural protein 3AB in picornaviruses.…”

Section: Coronavirus N Proteinmentioning

confidence: 58%

“…Poliovirus 3AB was the first RNA chaperone described in picornaviruses (DeStefano and Titilope, 2006). Domain organization and disorder prediction analyses showed that poliovirus or EV71 protein 3AB does not contain any intrinsically disordered regions, implying that the entropy transfer mechanism does not apply to enteroviral 3AB (Tang et al, 2014). However, the RNA chaperone activity of 3AB was moderately inhibited by various divalent metallic ions, implying that 3AB remodels RNA molecules through transient ionic interactions with the negatively charged RNA backbone (Woodson, 2010).…”

Section: Coronavirus N Proteinmentioning

confidence: 99%

“…However, the RNA chaperone activity of 3AB was moderately inhibited by various divalent metallic ions, implying that 3AB remodels RNA molecules through transient ionic interactions with the negatively charged RNA backbone (Woodson, 2010). The studies by Gangaramani et al and Tang et al have reported that the 3B region plus the C-terminal 7 a.a. of protein 3A is the key region for the RNA chaperone activity of 3AB (Gangaramani et al, 2010;Tang et al, 2014). Moreover, residues Lys-81, Phe-83, His-86, Tyr-90 and Arg-104 of 3AB have been reported to be critical for the RNA chaperone activity of poliovirus or EV71 3AB (Gangaramani et al, 2010;Tang et al, 2014).…”

Section: Coronavirus N Proteinmentioning

confidence: 99%

See 1 more Smart Citation

RNA chaperones encoded by RNA viruses

Yang

Xia

et al. 2015

Virol. Sin.

Self Cite

View full text Add to dashboard Cite

RNAs are functionally diverse macromolecules whose proper functions rely strictly upon their correct tertiary structures. However, because of their high structural flexibility, correct folding of RNAs is challenging and slow. Therefore, cells and viruses encode a variety of RNA remodeling proteins, including helicases and RNA chaperones. In RNA viruses, these proteins are believed to play pivotal roles in all the processes involving viral RNAs during the life cycle. RNA helicases have been studied extensively for decades, whereas RNA chaperones, particularly virus-encoded RNA chaperones, are often overlooked. This review describes the activities of RNA chaperones encoded by RNA viruses, particularly the ones identified and characterized in recent years, and the functions of these proteins in different steps of viral life cycles, and presents an overview of this unique group of proteins.

show abstract

“…Moreover, 3B and the last seven amino acids at the C-terminal of 3A (termed 3B ? 7) possess RNA chaperone activity, and five amino acids, i.e., Lys-80, Phe-82, Phe-85, Tyr-89, and Arg-103, are critical and probably the active sites of 3AB for its RNA chaperone activity (Tang et al 2014). The Golgi resident protein acylcoenzyme A binding domain-containing 3 (ACBD3) promotes EV71 replication by interacting with the 3A protein (Fig.…”

Section: A Proteinmentioning

confidence: 99%

Recent Progress on Functional Genomics Research of Enterovirus 71

Wang

2018

Virol. Sin.

View full text Add to dashboard Cite

Enterovirus 71 (EV71) is one of the main pathogens that causes hand-foot-and-mouth disease (HFMD). HFMD caused by EV71 infection is mostly self-limited; however, some infections can cause severe neurological diseases, such as aseptic meningitis, brain stem encephalitis, and even death. There are still no effective clinical drugs used for the prevention and treatment of HFMD. Studying EV71 protein function is essential for elucidating the EV71 replication process and developing anti-EV71 drugs and vaccines. In this review, we summarized the recent progress in the studies of EV71 noncoding regions (5 0 UTR and 3 0 UTR) and all structural and nonstructural proteins, especially the key motifs involving in viral infection, replication, and immune regulation. This review will promote our understanding of EV71 virus replication and pathogenesis, and will facilitate the development of novel drugs or vaccines to treat EV71.

show abstract

The identification and characterization of nucleic acid chaperone activity of human enterovirus 71 nonstructural protein 3AB

Cited by 10 publications

References 50 publications

Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone

Human Enterovirus Nonstructural Protein 2CATPase Functions as Both an RNA Helicase and ATP-Independent RNA Chaperone

RNA chaperones encoded by RNA viruses

Recent Progress on Functional Genomics Research of Enterovirus 71

Contact Info

Product

Resources

About