SART3-Dependent Accumulation of Incomplete Spliceosomal snRNPs in Cajal Bodies

Cajal bodies (CBs) are evolutionarily conserved nuclear structures involved in the metabolism of spliceosomal small nuclear ribonucleoprotein particles (snRNPs). CBs are not present in all cell types, and the trigger for their formation is not yet known. Here, we depleted cells of factors required for the final steps of snRNP assembly and assayed for the presence of stalled intermediates in CBs. We show that depletion induces formation of CBs in cells that normally lack these nuclear compartments, suggesting that CB nucleation is triggered by an imbalance in snRNP assembly. Accumulation of stalled intermediates in CBs depends on the di-snRNP assembly factor SART3. SART3 is required for both the induction of CB formation as well as the tethering of incomplete snRNPs to coilin, the CB scaffolding protein. We propose a model wherein SART3 monitors tri-snRNP assembly and sequesters incomplete particles in CBs, thereby allowing cells to maintain a homeostatic balance of mature snRNPs in the nucleoplasm. [Display omitted] •Inhibition of snRNP assembly induces new Cajal bodies•Stalled snRNP assembly intermediates accumulate in Cajal bodies•SART3 interacts with coilin and anchors incomplete snRNPs to Cajal bodies•SART3 and Cajal bodies survey snRNP assembly Cajal bodies are nonubiquitous nuclear structures involved in snRNP biogenesis. Novotný et al. demonstrate that Cajal body formation is triggered by inhibition of snRNP assembly. Stalled assembly intermediates highly accumulate in these bodies, which indicate that Cajal bodies are involved in quality control of snRNP assembly.