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THO/Sub2p functions to coordinate 3'-end processing with gene-nuclear pore association.
Mathieu Rougemaille1, Guennaelle Dieppois, Elena Kisseleva-Romanova
1LEA Laboratory of Nuclear RNA metabolism, Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique - UPR2167, 1, av de la Terrasse, 91190, Gif sur Yvette, France.
The THO complex and Sub2p helicase are crucial for messenger ribonucleoprotein particle (mRNP) biogenesis. Mutations stall mRNP export, revealing THO/Sub2p
Area of Science:
- Molecular Biology
- Gene Expression
- RNA Processing
Background:
- Messenger ribonucleoprotein particles (mRNPs) form during transcription.
- The THO complex and Sub2p helicase are involved in transcription and mRNP biogenesis.
- Their precise roles in these processes are not fully understood.
Purpose of the Study:
- To elucidate the function of the THO complex/Sub2p in mRNP biogenesis and gene expression.
- To identify genes regulated by the THO complex/Sub2p.
- To determine the specific step at which THO/Sub2p acts in mRNP maturation.
Main Methods:
- Analysis of THO/Sub2p mutants in yeast.
- Characterization of stalled mRNP intermediates.
- Microarray analysis of gene expression.
- Localization studies of nuclear pore and polyadenylation factors.
Main Results:
- THO/Sub2p mutations cause stalled mRNP intermediates containing nuclear pore and polyadenylation factors associated with chromatin.
- Microarray analysis identified approximately 400 novel target genes requiring THO/Sub2p for expression.
- These target genes are aberrantly docked to the nuclear pore in mutants.
Conclusions:
- The THO complex/Sub2p is essential for coordinating events that lead to mRNP export competence.
- This function is required after commitment to 3'-processing but before nuclear export.
- THO/Sub2p plays a critical role in ensuring efficient gene expression by facilitating mRNP maturation.
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