Virus Details


VHFID1955

Host Factor Information

Gene Name HNRNPA1
HF Protein Name Heterogeneous nuclear ribonucleoprotein A1
HF Function Required for translation and replication of enterovirus 71
Uniprot ID P09651
Protein Sequence View Fasta Sequence
NCBI Gene ID 3178
Host Factor (HF) Name in Paper HNRNPA1
Gene synonyms HNRPA1
Ensemble Gene ID ENSG00000135486
Ensemble Transcript ENST00000340913 [P09651-1];ENST00000546500 [P09651-2];ENST00000547276 [P09651-3];ENST00000547566 [P09651-2]
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0000381, GO:0000398, GO:0003697, GO:0003723, GO:0003727, GO:0005634, GO:0005654, GO:0005681, GO:0005737, GO:0006405, GO:0008543, GO:0016020, GO:0016032, GO:0016070, GO:0019904, GO:0030529, GO:0032211, GO:0032212, GO:0035198, GO:0036002, GO:0042149, GO:0042802, GO:0051028, GO:0051168, GO:0051170, GO:0061752, GO:0070062, GO:0071013, GO:0098505, GO:1903936,
MINT ID P09651
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 164017
PANTHER ID N.A.
PDB ID(s) 1HA1, 1L3K, 1PGZ, 1PO6, 1U1K, 1U1L, 1U1M, 1U1N, 1U1O, 1U1P, 1U1Q, 1U1R, 1UP1, 2H4M, 2LYV, 2UP1, 4YOE, 5MPG, 5MPL,
pfam ID PF11627, PF00076,
Drug Bank ID N.A.,
ChEMBL ID CHEMBL1955709
Organism Homo sapiens (Human)

Pathogen Information

Virus Name Enterovirus 71
Virus Short Name EV-71
Order Picornavirales
Virus Family Picornaviridae
Virus Subfamily N.A.
Genus Enterovirus
Species Enterovirus A
Host Human, mammals
Cell Tropism The gastrointestinal trac
Associated Disease Hand, foot and mouth disease, meningitis
Mode of Transmission Either fecal-oral or respiratory
VIPR DB link https://www.viprbrc.org/brc/home.spg?decorator=picorna
ICTV DB link https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/234/picornaviridae
Virus Host DB link http://www.genome.jp/virushostdb/view/?virus_lineage=Picornaviridae

Publication Information

Paper Title High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71
Author's Name Jeffrey D. Levengood, Michele Tolbert, Mei-Ling Li and Blanton s. Tolbert
Journal Name RNA biology
Pubmed ID 23727900
Abstract Human Enterovirus 71 (EV71) is an emerging pathogen of infectious disease and a serious threat to public health. Currently, there are no antivirals or vaccines to slow down or prevent EV71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. EV71 uses a type I internal ribosome entry site (IRES) to recruit the 40S ribosomal subunit via a pathway that requires the cytoplasmic localization of hnRNP A1, which acts as an IRES trans-activating factor. The mechanism of how hnRNPA1 trans activates EV71 RNA translation is unknown, however. Here, we report that the UP1 domain of hnRNP A1 interacts specifically with stem loop II (SLII) of the IRES, via a thermodynamically well-defined biphasic transition that involves conserved bulge 5-AYAGY-3 and hairpin 5-RY(U/A)CCA-3 loops. Calorimetric titrations of wild-type and mutant SLII constructs reveal these structural elements are essential to form a high-affinity UP1-SLII complex. Mutations that alter the bulge and hairpin primary or secondary structures abrogate the biphasic transition and destabilize the complex. Notably, mutations within the bulge that destabilize the complex correlate with a large reduction in IRES-dependent translational activity and impair EV71 replication. Taken together, this study shows that a conservedSLII structure is necessary to form a functional hnRNP A1-IRES complex, suggesting that small molecules that target this stem loop may have novel antiviral properties.
Used Model HeLa cells
DOI 10.4161/rna.25107