Fig. 8: Model for transcription termination-dependent snoRNA shuttling.

After the transcription by RNAP II, pre-snoRNAs undergo two different maturation pathways depending on their transcription termination. While the majority of snoRNAs is terminated by the NNS complex, snoRNAs that escape the NNS termination sites are terminated further downstream by the CPF-CF machinery. The NNS-terminated snoRNAs are mostly oligoadenylated, whereas CPF-CF terminated snoRNAs own a poly(A) tail. Coupled to the NNS termination, core proteins are loaded co- or post-transcriptionally, assisted by various assembly factors. Lhp1, as well as the Lsm2-8 complex, binds to the oligo(U) tract at the 3’-end of pre-snoRNAs, and oligoadenylated snoRNAs are rapidly processed in the nucleus. Besides the core protein Snu13, several guard proteins such as Gbp2, Npl3, Hrp1, and Nab2 associate with CPF-CF-terminated snoRNAs and recruit the export receptor Mex67-Mtr2 heterodimer for the nuclear export. Lhp1 and Lsm2-8 complex also bind to the CPF-CF-terminated snoRNAs. Similar to the guard proteins, Lhp1 can also recruit Mex67-Mtr2. During the cytoplasmic phase, the Mex67-Mtr2 and guard proteins dissociate. Lhp1 and Lsm2-8 remain bound to the pre-snoRNAs to protect them and to allow the binding of the import receptors Cse1 and Mtr10 to the Lsm-ring, to mediate the re-import. Subsequently, the remaining core proteins, such as Nop1, assemble with the CPF-CF-terminated snoRNAs. The assembly factors, Lhp1 and Lsm2-8, leave the snoRNPs to allow the final 3’-end trimming by the nuclear, Rrp6-containing exosome. Finally, mature snoRNPs reside in their final destination, the nucleolus. RNAP II = RNA polymerase II.