Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The mRNA export adaptor Yra1p/REF is crucial for nascent messenger ribonucleoprotein (mRNP) assembly and export receptor recruitment.
• Yra1p deficiency leads to mRNA export blockages and reduced levels of specific transcripts, including reporter genes like LacZ.

Purpose of the Study:

• To investigate the role of Mlp1p/Mlp2p proteins in mitigating mRNA export defects caused by Yra1p mutations.
• To elucidate the regulatory mechanisms by which Mlps influence mRNA levels and transcription in the context of mRNA export.

Main Methods:

• Utilized Yra1p and Mlp1p/Mlp2p mutant strains in yeast.
• Employed techniques including LacZ reporter assays, quantitative FISH, pulse-chase experiments, and microarray analysis.
• Performed genetic interaction studies with Nab2p, another mRNA-binding protein.

Main Results:

• Loss of Mlp1p/Mlp2p restored LacZ mRNA levels and cytoplasmic localization in Yra1p mutants, but did not rescue bulk mRNA export.
• Chromatin immunoprecipitation and FISH revealed that Mlps actively downregulate LacZ mRNA synthesis in Yra1p mutants.
• Microarray data indicated Mlp2p's role in reducing a subset of cellular transcripts in Yra1p mutants.
• Yra1p interacts with Nab2p, and Mlp deletion rescues growth defects in yra1 and nab2 mutants.

Conclusions:

• Mlps act as a regulatory platform at the nuclear pore, downregulating transcription of specific genes when mRNA export is impaired.
• Yra1p and Nab2p are essential for proper mRNP docking to the Mlp platform.
• The findings suggest that Mlps integrate mRNA transcription and export, providing a feedback mechanism to control gene expression.