Proteomics

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Evolutionarily conserved spliceosome-exosome pathway in nuclear mRNA surveillance


ABSTRACT: Intron-containing mRNAs are co-transcriptionally 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 or cytoplasmic export. The human LENG8-PCID2 complex operates as an mRNP-decay connector, coupling nuclear mRNPs to the RNA-degrading exosome via the PAXT adaptor complex, while the related GANP-PCID2 complex connects mRNPs to the nuclear pore complex. Both recognize the mRNP component UAP56, but LENG8-PCID2 uniquely associates with early splicing factors through a direct interaction with U1A and RRP1B. Notably, the Thp3-Csn12 ortholog in budding yeast also serves as an mRNP-decay connector, coupling 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.

INSTRUMENT(S):

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Barbara Steigenberger  

LAB HEAD: Elena Conti

PROVIDER: PXD071678 | Pride | 2026-05-18

REPOSITORIES: Pride

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