Poly(A)-specific ribonuclease is a nuclear ribosome biogenesis factor involved in human 18S rRNA maturation

Christian Montellese1, Nathalie Montel-Lehry2, Anthony K Henras2

  • 1Institut für Biochemie, ETH Zurich, Zurich CH-8093, Switzerland.

Nucleic Acids Research
|April 13, 2017
PubMed

Insights

Poly-A specific ribonuclease (PARN) is crucial for processing 18S ribosomal RNA (rRNA), a key step in ribosome biogenesis. This finding links PARN

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Poly-A specific ribonuclease (PARN) is known for its role in mRNA degradation and non-coding RNA processing.
  • Mutations in PARN are associated with human diseases like dyskeratosis congenita and pulmonary fibrosis.
  • The precise function of PARN in ribosome biogenesis was previously uncharacterized.

Purpose of the Study:

  • To investigate the role of PARN in the maturation of human 18S ribosomal RNA (rRNA).
  • To elucidate the mechanism by which PARN contributes to ribosome biogenesis.
  • To explore the potential link between PARN's function in ribosome biogenesis and associated pathologies.

Main Methods:

  • Depletion of PARN and expression of catalytically inactive PARN mutants in human cells.
  • Analysis of 18S rRNA processing intermediates using biochemical and molecular techniques.
  • In vitro processing assays with recombinant PARN and ITS1 RNA fragments.
  • Co-purification studies with 40S ribosomal subunit precursors.

Main Results:

  • PARN is essential for the production of 40S ribosomal subunits and localizes to the nucleolus.
  • PARN depletion or inactivation leads to the accumulation of 3'-extended 18S rRNA precursors.
  • PARN functions in the 3' to 5' exonucleolytic trimming of the ITS1 region of 18S rRNA precursors.
  • PARN acts upstream of NOB1-mediated cleavage in the cytoplasm.

Conclusions:

  • PARN is identified as a novel component of the human ribosome biogenesis machinery.
  • PARN's role in 18S rRNA processing is critical for 40S subunit maturation.
  • Defects in ribosome biogenesis due to impaired PARN function may underlie PARN-associated diseases.

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