The spliceosome is an RNA-protein complex, comprised of small nuclear ribonucleoprotein particles (snRNPs), that mediates the removal of introns from pre-mRNA to generate mature mRNA. Formation and regulation of the spliceosome requires assistance from spliceosome-interacting proteins, including the multifunctional protein SART3, which has previously been shown to interact with and mediate recycling of spliceosome U6 snRNPs. In this study (Klimešová et al., 2023), David Staněk and colleagues show that SART3 also interacts with U2 snRNP. Using immunoprecipitation and gradient centrifugation assays, the authors show that SART3 associates with the U2 snRNP via its N-terminal HAT domain and that this interaction occurs within the post-splicing complex, which contains U2, U5 and U6 snRNPs. In addition, the authors find that SART3 interacts with the RNA helicase DHX15, which disassembles post-splicing complexes, and downregulation of DHX15 reduces association of SART3 with U2 snRNP. Taken together, these data suggest a modified model of SART3-mediated spliceosome recycling, whereby SART3 localises to the post-splicing complex via DHX15 and U2 snRNP, where it can interact with U6 snRNA to protect it from degradation and promote its recycling for the next round of splicing.
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