Nuclear pore components affect distinct stages of intron-containing gene expression

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Nuclear pore-associated factors, like SUMO-protease Ulp1, are implicated in preventing export of intron-containing messenger ribonucleoparticles (mRNPs).
• The precise molecular mechanisms and sumoylated targets of Ulp1 in mRNA quality control remain largely unknown.

Purpose of the Study:

• To investigate the role of the THO complex and Ulp1 in nuclear pore-dependent mRNA quality control.
• To elucidate the mechanisms by which nuclear pores regulate the expression of intron-containing genes.

Main Methods:

• Utilized yeast models to study gene expression phenotypes.
• Performed epistasis analyses to determine the order of function for nuclear pore components.
• Investigated the impact of sumoylation mutants and Ulp1 inactivation on reporter gene expression.

Main Results:

• Inactivation of ULP1 and sumoylation mutants of the THO complex share a similar phenotype, but do not cause true 'pre-mRNA leakage'.
• THO complex activity alterations differentially affect intronless and intron-containing reporter gene expression.
• Introns within THO target genes can attenuate the impact of THO inactivation on transcription.
• Nuclear pore components Ulp1 and Mlp1/Pml39 act at distinct stages in regulating intron-containing gene expression.

Conclusions:

• Nuclear pores employ multiple mechanisms to ensure proper gene expression.
• Intronic sequences can mitigate early mRNP biogenesis defects, highlighting a novel aspect of mRNA quality control.