Evolutionarily conserved spliceosome-exosome pathway in nuclear mRNA surveillance

Area of Science:

• Molecular Biology
• RNA Biology
• Cellular Surveillance

Background:

• Intron-containing messenger RNAs (mRNAs) undergo cotranscriptional splicing and assembly into messenger ribonucleoprotein (mRNP) particles.
• Cellular surveillance pathways monitor mRNP biogenesis, directing them towards either nuclear degradation or cytoplasmic export.

Purpose of the Study:

• To elucidate the mechanisms governing the sorting of mRNPs between nuclear degradation and cytoplasmic export.
• To identify the molecular players involved in coupling mRNPs to nuclear degradation pathways.

Main Methods:

• Biochemical approaches
• Structural biology techniques
• Analysis of protein-protein interactions

Main Results:

• The LENG8-PCID2 complex acts as an mRNP decay connector, linking nuclear mRNPs to the RNA-degrading exosome via the PAXT adaptor complex.
• LENG8-PCID2 interacts with the mRNP component UAP56 and early splicing factors U1A and RRP1B.
• A conserved pathway involving Thp3-Csn12 and Mud2-Bbp in budding yeast couples early splicing factors to the nuclear exosome.

Conclusions:

• A novel spliceosome-exosome mRNP decay pathway has been uncovered.
• This pathway demonstrates striking evolutionary conservation in molecular principles between humans and budding yeast.
• The findings reveal conserved mechanisms for RNA quality control during mRNP biogenesis.