In eukaryotes, U-rich small nuclear RNAs (snRNAs) are integral components of spliceosomes, the cellular machines that mediate the splicing of nascent mRNA. Before their incorporation into spliceosomal particles, snRNAs must be transiently exported to the cytoplasm, where part of their maturation takes place. Although the complex mediating snRNA nuclear export was first identified 25 years ago, the molecular details of its function and assembly have remained unclear.
Scientists from the IBS EPIGEN group, in collaboration with EMBL Grenoble and Aarhus University, used cryo-electron microscopy together with biochemical and cellular assays to obtain a detailed characterization of the snRNA export machinery. It comprises the nuclear cap-binding complex (CBC ; subunits CBP20 and CBP80) bound to 5′-capped RNA, the nuclear export receptor CRM1–RanGTP, and the phosphorylated RNA effector PHAX.
The obtained structure reveals a synergistic assembly that requires the interaction of all components. PHAX plays a central role : it acts as an intermediary between the CBC, the export factor CRM1, and the CBC-bound capped RNA, thereby preventing the recruitment of degradation factors. Moreover, the phosphorylated region of PHAX interacts with RanGTP, which blocks the nonspecific association of other RNAs at this interface.
These results provide the first detailed structural insight into the role of the CBC in directing nascent RNAs toward a specific biogenesis pathway, namely nuclear export.
Structural basis for the synergistic assembly of the snRNA export complex. Dubiez E, Garland W, Finderup Brask M, Boeri Erba E, Heick Jensen T, Kadlec J, Cusack S. Nature Structural & Molecular Biology 2025 ; 1555-1566.
Contact : Jan Kadlec (IBS/Epigenetics and molecular pathways Group)