Picornavirus IRES elements: RNA structure and host protein interactions

Martínez‐Salas, Encarnación; Francisco‐Velilla, Rosario; Fernandez-Chamorro, Javier; Lozano, Gloria; Díaz-Toledano, Rosa

doi:10.1016/j.virusres.2015.01.012

Cited by 108 publications

(126 citation statements)

References 183 publications

(176 reference statements)

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…The HRV IRES is type I, EMCV and FMDV are type II and the HCV IRES is classed as a type III (Belsham, 2009;Martínez-Salas et al, 2015;Tsukiyama-Kohara et al, 1992). For all constructs there was a modest, non-significant inhibition of cap-mediated translation in the presence of an increasing concentration of PIK93 (0-5 µM) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The genome is flanked by 5¢ and 3¢ UTRs and is polyadenylated. The 5¢ UTR contains a number of structural regions: a long-hairpin 'S-fragment' structure, a poly-C tract, a region containing pseudoknots, the cis-acting replicative element (cre) and the internal ribosome entry site (IRES), involved in 7-methyl-guanosine 'cap'-independent translation (Belsham & Brangwyn, 1990;Martínez-Salas et al, 2015). The coding region is separated into four regions: L Pro , P1, P2 and P3.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

Loundras

Herod

Harris

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

Foot-and-mouth disease virus (FMDV) causes economically damaging infections of clovenhooved animals, with outbreaks resulting in large financial losses to the agricultural industry. Due to the highly contagious nature of FMDV, research with infectious virus is restricted to a limited number of key facilities worldwide. FMDV sub-genomic replicons are therefore important tools for the study of viral translation and genome replication. The type III phosphatidylinositol-4-kinases (PI4Ks) are a family of enzymes that plays a key role in the production of replication complexes (viral factories) of a number of positive-sense RNA viruses and represents a potential target for novel pan-viral therapeutics. Here, we investigated whether type III PI4Ks also play a role in the FMDV life cycle, using a combination of FMDV sub-genomic replicons and bicistronic internal ribosome entry site (IRES)-containing reporter plasmids. We demonstrated that replication of the FMDV replicon was unaffected by inhibitors of either PI4KIIIa or PI4KIIIb. However, PIK93, an inhibitor previously demonstrated to target PI4KIIIb, did inhibit IRES-mediated protein translation. Consistent with this, cells transfected with FMDV replicons did not exhibit elevated levels of phosphatidylinositol-4-phosphate lipids. These results are therefore supportive of the hypothesis that FMDV genome replication does not require type III PI4K activity and does not activate these kinases.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

Loundras

Herod

Harris

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…IRES function depends on the interaction with host factors [17,20]. In turn, these factors interact within the cell with other proteins, which can influence IRES activity by indirect interactions.…”

Section: Rna-affinity Methods To Study Ires-protein Interactionsmentioning

confidence: 99%

“…These elements are diverse in primary sequence and secondary RNA structure, being classified into five different types [16]. Functionally related picornavirus IRESs harbor a common RNA structure core and sequence motifs maintained by evolutionary conserved covariant substitutions [17]. Assembly of 48S initiation complexes into IRESs of entero-, cardio-, and aphthovirus requires eIF4G, eIF4A, eIF1, eIF3 and the ternary complex.…”

Section: Introductionmentioning

confidence: 99%

RNA–protein interaction methods to study viral IRES elements

Francisco‐Velilla

Fernandez-Chamorro

Lozano

et al. 2015

Methods

Self Cite

View full text Add to dashboard Cite

a b s t r a c tTranslation control often takes place through the mRNA untranslated regions, involving direct interactions with RNA-binding proteins (RBPs). Internal ribosome entry site elements (IRESs) are cis-acting RNA regions that promote translation initiation using a cap-independent mechanism. A subset of positive-strand RNA viruses harbor IRESs as a strategy to ensure efficient viral protein synthesis. IRESs are organized in modular structural domains with a division of functions. However, viral IRESs vary in nucleotide sequence, secondary RNA structure, and transacting factor requirements. Therefore, in-depth studies are needed to understand how distinct types of viral IRESs perform their function. In this review we describe methods to isolate and identify RNA-binding proteins important for IRES activity, and to study the impact of RNA structure and RNA-protein interactions on IRES activity.

show abstract

“…This structured region of RNA interacts with both canonical translation initiation factors and other host proteins known as IRES transacting factors (ITAFs) to recruit ribosomes to viral RNA (7–9). To date, a number of host proteins have been proposed to act as ITAFs for picornavirus translation, including the established ITAFs polypyrimidine tract-binding protein (PTB), poly(rC)-binding proteins 1 and 2 (PCBP1/2), upstream of N-ras (Unr), lupus La protein (La), nucleolin, and serine- and arginine-rich splicing factor 3 (SRSF3 or SRp20) (7, 9). In addition, three host proteins have been identified that restrict picornavirus translation: double-stranded RNA binding protein 76 (DRBP76), K homology-type RNA splicing regulatory protein (KHSRP, KSRP, or FBP2), and AU-rich element degradation factor 1 (AUF1 or hnRNP D).…”

Section: Introductionmentioning

confidence: 99%

Direct and Indirect Effects on Viral Translation and RNA Replication Are Required for AUF1 Restriction of Enterovirus Infections in Human Cells

Ullmer

Semler

2018

mBio

View full text Add to dashboard Cite

Picornaviruses primarily infect the gastrointestinal or upper respiratory tracts of humans and animals and may disseminate to tissues of the central nervous system, heart, skin, liver, or pancreas. Many common human pathogens belong to the Picornaviridae family, which includes viruses known to cause paralytic poliomyelitis (poliovirus); myocarditis (coxsackievirus B3 [CVB3]); the common cold (human rhinovirus [HRV]); and hand, foot, and mouth disease (enterovirus 71 [EV71]), among other illnesses. There are no specific treatments for infection, and vaccines exist for only two picornaviruses: poliovirus and hepatitis A virus. Given the worldwide distribution and prevalence of picornaviruses, it is important to gain insight into the host mechanisms used to restrict infection. Other than proteins involved in the innate immune response, few host factors have been identified that restrict picornavirus replication. The work presented here seeks to define the mechanism of action for the host restriction factor AUF1 during infection by poliovirus and CVB3.

show abstract

Picornavirus IRES elements: RNA structure and host protein interactions

Cited by 108 publications

References 183 publications

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases

RNA–protein interaction methods to study viral IRES elements

Direct and Indirect Effects on Viral Translation and RNA Replication Are Required for AUF1 Restriction of Enterovirus Infections in Human Cells

Contact Info

Product

Resources

About