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UFMylation anchors splicing factors at the ER to reprogram nuclear splicing

ABSTRACT: How organelles communicate stress to the nucleus to coordinate adaptive responses remains a fundamental question in cell biology. Here, we identify a non-canonical retrograde signaling pathway in which stalling-induced UFMylation of ER-associated ribosomes anchors splicing regulators at the ER, directly coupling translational stress to nuclear RNA processing. Phylogenetic profiling linked the UFMylation machinery to a network of nuclear mRNA processing factors. Fractionation-based quantitative proteomics revealed that translational stress triggers UFM1-dependent retention of serine/arginine-rich (SR) splicing factors at the ER, depleting their nuclear pools. Mechanistically, UFMylated ribosomes physically tether SR proteins at the ER surface, driving widespread intron retention that preferentially targets transcripts encoding ER membrane and trafficking components—a response conserved from plants to mammals. These findings reframe UFMylation from a local ribosome repair signal to a systems-level coordinator of ER-nucleus communication that reprograms nuclear splicing and reshapes membrane-associated gene expression with implications for neurodegenerative diseases linked to UFMylation defects.

ORGANISM(S): Arabidopsis thaliana Mus musculus Homo sapiens

PROVIDER: GSE325905 | GEO | 2026/03/27

REPOSITORIES: GEO

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The Nuclear-retained non-coding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation

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