Nuclear Pre-snRNA Export Is an Essential Quality Assurance Mechanism for Functional Spliceosomes

摘要

Removal of introns from pre-mRNAs is an essentialstep in eukaryotic gene expression, mediated byspliceosomes that contain snRNAs as key components.Although snRNAs are transcribed in the nucleusand function in the same compartment, allexcept U6 shuttle to the cytoplasm. Surprisingly,the physiological relevance for shuttling is unclear,in particular because the snRNAs in Saccharomycescerevisiae were reported to remain nuclear. Here, weshow that all yeast pre-snRNAs including U6 undergoa stepwise maturation process after nuclearexport by Mex67 and Xpo1. Sm- and Lsm-ringattachment occurs in the cytoplasm and is importantfor the snRNA re-import, mediated by Cse1 andMtr10. Finally, nuclear pre-snRNA cleavage and trimethylationof the 50-cap finalizes shuttling. Importantly,preventing pre-snRNAs from being exportedor processed results in faulty spliceosome assemblyand subsequent genome-wide splicing defects.Thus, pre-snRNA export is obligatory for functionalsplicing and resembles an essential evolutionarilyconserved quality assurance step.