Evolutionarily conserved spliceosome–exosome pathway in nuclear mRNA surveillance

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.