Related Experiment Video
Updated: May 17, 2026

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
Published on: September 15, 2021
Evolutionarily conserved spliceosome-exosome pathway in nuclear mRNA surveillance
Daniel K Abbas1, Fabien Bonneau1, Max E Wilkinson2
1Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Munich 82152, Germany.
Abstract:
Intron-containing mRNAs are cotranscriptionally spliced and assembled into messenger ribonucleoprotein (mRNP) particles, a process monitored by surveillance pathways. Here, we combined biochemical and structural approaches to elucidate the mechanisms by which mRNPs are sorted between two opposing fates: nuclear degradation and cytoplasmic export. While the human GANP-PCID2 complex is known to connect mRNPs to nuclear export, our data indicate that the LENG8-PCID2 complex operates as an mRNP decay connector, coupling nuclear mRNPs to the RNA-degrading exosome via the PAXT adaptor complex. Both recognize the mRNP component UAP56, but LENG8-PCID2 uniquely associates with early splicing factors through a direct interaction with U1A and RRP1B. Similarly, the Thp3-Csn12 ortholog in budding yeast couples the early splicing factors Mud2-Bbp with the nuclear exosome. The spliceosome-exosome mRNP decay pathway we uncovered reveals molecular principles that remain strikingly conserved across evolution, despite the fundamental differences in splicing and decay between humans and budding yeast.
Insights
The LENG8-PCID2 complex connects nuclear messenger ribonucleoprotein (mRNP) particles to the exosome for degradation, revealing a conserved spliceosome-exosome decay pathway. This pathway ensures proper RNA processing and nuclear export.
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.
Related Concept Videos
Nuclear Export of mRNA
Nuclear Export of mRNA
Nonsense-mediated mRNA Decay
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Nonsense-mediated mRNA Decay
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
RNA Splicing
RNA Splicing
