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

TL;DR

This study shows how certain snoRNAs shuttle into the cytoplasm based on how they are transcribed and protected by specific proteins.

Contribution

The study identifies a transcription termination-dependent mechanism for snoRNA export, mediated by mRNA guard proteins.

Findings

CPF-CF termination leads to snoRNA polyadenylation and cytoplasmic export via Hrp1 and Nab2.

NNS termination results in nuclear retention of snoRNAs.

Re-imported CPF-CF-terminated snoRNAs form functional snoRNPs.

Abstract

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.

snoRNAs are synthesized and function in the nucleus, but some of them shuttle into the cytoplasm. This study reveals that the mode of transcription, specifically CPF-CF termination, determines whether the snoRNA is exported.

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