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) |
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 |
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 |