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Updated: Jul 25, 2025

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
The RNA-binding protein ZC3H11A interacts with the nuclear poly(A)-binding protein PABPN1 and alters polyadenylation
Katharina Kases1, Erik Schubert1, Zamaneh Hajikhezri1
1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Abstract:
Nuclear mRNA metabolism is regulated by multiple proteins, which either directly bind to RNA or form multiprotein complexes. The RNA-binding protein ZC3H11A is involved in nuclear mRNA export, NF-κB signaling, and is essential during mouse embryo development. Furthermore, previous studies have shown that ZC3H11A is important for nuclear-replicating viruses. However, detailed biochemical characterization of the ZC3H11A protein has been lacking. In this study, we established the ZC3H11A protein interactome in human and mouse cells. We demonstrate that the nuclear poly(A)-binding protein PABPN1 interacts specifically with the ZC3H11A protein and controls ZC3H11A localization into nuclear speckles. We report that ZC3H11A specifically interacts with the human adenovirus type 5 (HAdV-5) capsid mRNA in a PABPN1-dependent manner. Notably, ZC3H11A uses the same zinc finger motifs to interact with PABPN1 and viral mRNA. Further, we demonstrate that the lack of ZC3H11A alters the polyadenylation of HAdV-5 capsid mRNA. Taken together, our results suggest that the ZC3H11A protein may act as a novel regulator of polyadenylation of nuclear mRNA.
Insights
The RNA-binding protein ZC3H11A interacts with PABPN1 and viral mRNA, regulating nuclear mRNA polyadenylation. This study reveals ZC3H11A
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Nuclear mRNA metabolism involves protein regulation and complex formation.
- ZC3H11A is an RNA-binding protein crucial for mRNA export, signaling, and development.
- ZC3H11A's role in nuclear-replicating viruses is known, but biochemical details are scarce.
Purpose of the Study:
- To biochemically characterize the ZC3H11A protein.
- To identify ZC3H11A interacting partners and elucidate its function in nuclear mRNA metabolism.
- To investigate ZC3H11A's role in viral mRNA processing.
Main Methods:
- Proteomics: Established the ZC3H11A protein interactome in human and mouse cells.
- Biochemical assays: Demonstrated specific interactions between ZC3H11A, PABPN1, and viral mRNA.
- Functional assays: Assessed the impact of ZC3H11A on viral mRNA polyadenylation.
Main Results:
- Identified PABPN1 as a specific interactor of ZC3H11A, controlling its nuclear speckle localization.
- Showed ZC3H11A interacts with human adenovirus type 5 (HAdV-5) capsid mRNA via shared zinc finger motifs, dependent on PABPN1.
- Demonstrated that ZC3H11A deficiency alters HAdV-5 capsid mRNA polyadenylation.
Conclusions:
- ZC3H11A interacts with PABPN1 and viral mRNA using conserved structural motifs.
- ZC3H11A plays a PABPN1-dependent role in regulating the polyadenylation of nuclear viral mRNA.
- ZC3H11A emerges as a potential novel regulator of nuclear mRNA polyadenylation.
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