Unknown

Dataset Information

0

High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71.


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 hnRNP A1 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 conserved SLII 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.

SUBMITTER: Levengood JD 

PROVIDER: S-EPMC3849161 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71.

Levengood Jeffrey D JD   Tolbert Michele M   Li Mei-Ling ML   Tolbert Blanton S BS  

RNA biology 20130522 7


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 fa  ...[more]

Similar Datasets

| S-EPMC5610934 | biostudies-literature
| S-EPMC3360637 | biostudies-literature
| S-EPMC4379574 | biostudies-literature
| S-EPMC5071646 | biostudies-literature
| S-EPMC5416833 | biostudies-literature
| S-EPMC6326802 | biostudies-literature
| S-EPMC5996053 | biostudies-literature
| S-EPMC5016833 | biostudies-literature
| S-EPMC5435352 | biostudies-other
| S-EPMC6069798 | biostudies-literature