A putative ubiquitin ligase required for efficient mRNA export differentially affects hnRNP transport
K Duncan1, J G Umen, C Guthrie
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448, USA.
Current Biology : CB
|June 30, 2000
Summary
Tom1p, a ubiquitin ligase, is crucial for efficient mRNA export in yeast, specifically impacting Nab2p-mRNA export. This suggests distinct mRNA export pathways regulated by the ubiquitin system.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Messenger RNAs (mRNAs) in the nucleus interact with heterogeneous nuclear ribonucleoproteins (hnRNPs).
- Shuttling hnRNPs facilitate mRNA export by bridging mRNA and transport machinery.
- The presence of multiple shuttling hnRNPs suggests specialized, regulated mRNA export pathways.
Purpose of the Study:
- To investigate the role of Tom1p, a conserved ubiquitin ligase, in mRNA export.
- To determine if Tom1p differentially affects hnRNP protein localization and export.
- To explore the existence of distinct mRNA export pathways.
Main Methods:
- Utilized Saccharomyces cerevisiae (S. cerevisiae) as a model organism.
- Generated tom1 mutations predicted to abolish ubiquitin ligase activity.
- Analyzed hnRNP protein localization and mRNA export efficiency via microscopy and biochemical assays.
Main Results:
- Tom1p is essential for efficient mRNA export in S. cerevisiae.
- Mutations in tom1 impair Nab2p-mRNA export, leading to nuclear accumulation of Nab2p-mRNA complexes near the nuclear pore complex (NPC).
- The export of other hnRNPs, such as Np13p, remains unaffected in tom1 mutants.
Conclusions:
- Tom1p's enzymatic activity differentially regulates the export of specific hnRNP proteins associated with mRNA.
- The findings support the existence of multiple mRNA export pathways.
- Export of Nab2p-associated mRNAs appears to depend on a specific branch of the ubiquitin protein modification pathway.
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