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The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and

Tomohiro Yamazaki1, Naoko Fujiwara, Hiroko Yukinaga

  • 1Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Molecular Biology of the Cell
|June 25, 2010
PubMed

Insights

Human RNA helicases UAP56 and URH49 form distinct mRNA export complexes, TREX and AREX, respectively. These complexes regulate different sets of genes, impacting mitosis at distinct stages.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Nuclear export of messenger RNA (mRNA) is crucial for eukaryotic gene expression.
  • The TREX complex links transcription, splicing, and mRNA export.
  • Yeast Sub2 protein diversified into human UAP56 and URH49 RNA helicases.

Purpose of the Study:

  • To investigate the distinct roles of human RNA helicases UAP56 and URH49 in mRNA export.
  • To characterize the protein complexes formed by UAP56 and URH49.
  • To determine the impact of these complexes on gene regulation and cellular processes, particularly mitosis.

Main Methods:

  • Proteomic analysis to identify protein complexes.
  • Genome-wide mRNA profiling to identify target mRNAs.
  • Depletion studies using RNA interference (RNAi) to assess functional consequences.
  • Phenotypic analysis of cellular defects, including mitotic progression and cytokinesis.

Main Results:

  • URH49 forms the alternative mRNA export (AREX) complex with CIP29, while UAP56 forms the human TREX complex.
  • UAP56 and URH49 regulate distinct sets of mRNAs genome-wide.
  • Depletion of UAP56 leads to mitotic delay and cohesion defects.
  • Depletion of URH49 results in chromosome arm resolution defects and failed cytokinesis.
  • Depletion of other TREX components or CIP29 phenocopies UAP56 or URH49 depletion, respectively.

Conclusions:

  • Human UAP56 and URH49 have evolved specialized functions in mRNA export.
  • These helicases form distinct complexes (TREX and AREX) that regulate different mRNA populations.
  • These distinct mRNA export pathways play critical, non-redundant roles in regulating mitosis at different stages.

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