Functional dissection of hnRNP D suggests that nuclear import is required before hnRNP D can modulate mRNA turnover

Chyi-Ying A Chen1, Nianhua Xu, Wenmiao Zhu

  • 1Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.

RNA (New York, N.Y.)
|March 24, 2004
PubMed

Insights

Nuclear import of hnRNP D (heterogeneous nuclear ribonucleoprotein D) is essential for its function in regulating cytoplasmic mRNA decay. Restoring nuclear entry in a mutant protein recovered its mRNA stabilizing activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • RNA Biology

Background:

  • Shuttling proteins play dual roles in the nucleus and cytoplasm.
  • The p37 isoform of hnRNP D regulates cytoplasmic mRNA decay.

Purpose of the Study:

  • To investigate the link between nuclear import of hnRNP D and its cytoplasmic function.
  • To determine if nuclear association with messenger ribonucleoprotein complexes (mRNPs) is necessary for cytoplasmic mRNA regulation.

Main Methods:

  • Utilizing a p37 mutant lacking the nuclear import signal.
  • Assessing mRNA decay rates in NIH3T3 cells.
  • Employing heterologous shuttling domains to restore nuclear entry.

Main Results:

  • The p37 isoform shuttles between the nucleus and cytoplasm.
  • A specific C-terminal domain mediates nuclear import.
  • A mutant lacking this domain, confined to the cytoplasm, lost its mRNA decay inhibitory function.
  • Restoring nuclear import via heterologous domains re-established cytoplasmic function.
  • hnRNP D association with target mRNAs requires nuclear entry.

Conclusions:

  • Nuclear import of hnRNP D is a prerequisite for its cytoplasmic function in mRNA decay.
  • This study establishes a model for understanding how "nuclear history" influences cytoplasmic mRNA fate.

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