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Optical Tweezers to Study RNA-Protein Interactions in Translation Regulation
Published on: February 12, 2022
Polypyrimidine Tract-Binding Protein Regulates Enterovirus 71 Translation Through Interaction with the Internal
Juemin Xi1, Fei Ye2, Guanzhou Wang2
1Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, 650118, China.
Insights
Polypyrimidine tract-binding protein 1 (PTB) binds to the Enterovirus 71 (EV71) internal ribosomal entry site (IRES). PTB positively regulates viral protein translation, offering insights into EV71 replication mechanisms.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Enterovirus 71 (EV71) causes hand, foot, and mouth disease outbreaks.
- Understanding EV71's life cycle requires knowledge of virus-host interactions.
- The EV71 5' untranslated region, including the IRES, is crucial for viral protein synthesis.
Purpose of the Study:
- To elucidate the molecular mechanisms of EV71-host interactions.
- To identify host factors involved in EV71 replication.
- To determine the role of polypyrimidine tract-binding protein 1 (PTB) in EV71 infection.
Main Methods:
- Investigated PTB binding to the EV71 IRES using biochemical assays.
- Identified specific PTB RNA recognition motifs (RRMs) involved in binding.
- Observed PTB subcellular localization changes upon EV71 infection.
- Utilized PTB knockdown to assess its effect on IRES activity and viral protein production.
Main Results:
- Polypyrimidine tract-binding protein 1 (PTB) directly binds to the EV71 internal ribosomal entry site (IRES).
- RNA recognition motifs 1 and 2 of PTB are essential for this interaction.
- EV71 infection induces the translocation of PTB from the nucleus to the cytoplasm.
- PTB knockdown significantly inhibits EV71 IRES activity and viral protein synthesis.
Conclusions:
- PTB is a host factor that interacts with the EV71 IRES.
- PTB positively regulates viral protein translation, playing a key role in EV71 replication.
- These findings contribute to understanding EV71 pathogenesis and potential therapeutic targets.
Abstract:
Enterovirus 71 (EV71), a major causative agent of hand, foot, and mouth disease, has caused periodic infection outbreaks in children in the Asia-Pacific region. In order to describe the largely unknown life cycle of EV71, the molecular basis of its virus-host interactions must first be determined. The 5' untranslated region of EV71 contains a cloverleaf-like structure and internal ribosomal entry site (IRES), which play an important role in transcription and translation of viral protein. We found that polypyrimidine tract-binding protein 1 (PTB) bound to the IRES of EV71. RNA recognition motifs 1 and 2 of PTB were responsible for its binding to the EV71 IRES. Moreover, PTB protein was shuttled from nucleus to cytoplasm after EV71 infection. Additionally, IRES activity and viral protein production were inhibited by PTB knockdown. These results suggest that PTB interacts with the EV71 IRES, and positively regulates viral protein translation.
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