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.

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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