CPF-CF-terminated snoRNAs shuttle through the cytoplasm via an mRNA guard protein-mediated surveillance mechanism

Although small nucleolar (sno)RNAs, which guide ribosomal (r)RNA modification, are synthesized and function in the nucleus, some of them can be detected in the cytoplasm. Here, we identify Mex67 and Xpo1 as snoRNP export receptors, and Mtr10 and Cse1 as their re-import factors. Interestingly, only a fraction of snoRNAs shuttle, and we reveal that the mode of transcription determines whether or not the snoRNA is exported. In Saccharomyces cerevisiae, RNA polymerase II-transcribed RNAs are terminated either via the Nrd1-Nab3-Sen1 (NNS) complex or the cleavage and polyadenylation factor (CPF-CF) complex. NNS termination, which mostly occurs for snoRNAs, leads to nuclear retention. Conversely, fail-safe CPF-CF termination results in transcript polyadenylation and subsequent association of the guard proteins Hrp1 and Nab2, which in turn mediate Mex67-Mtr2 dependent export. Importantly, re-imported CPF-CF-terminated snoRNAs form functional snoRNPs. Together, we identified that transcription termination mode determines snoRNA export through a guard protein-controlled mechanism.