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

**Authors:** Fei Yu, Gianluca Zaccagnini, Yawen Duan, Jan-Phillip Lamping, Sophie Tagnères, Katherine E. Bohnsack, Heike Krebber

PMC · DOI: 10.1038/s41467-026-70373-8 · 2026-03-06

## 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.

## Key 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.

## Linked entities

- **Genes:** NXF1 (nuclear RNA export factor 1) [NCBI Gene 10482], XPO1 (exportin 1) [NCBI Gene 7514], MTR10 (mRNA transport regulator MTR10) [NCBI Gene 854331], CSE1L (chromosome segregation 1 like) [NCBI Gene 1434], USP6 (ubiquitin specific peptidase 6) [NCBI Gene 9098], NAB2 (NGFI-A binding protein 2) [NCBI Gene 4665], NXT1 (nuclear transport factor 2 like export factor 1) [NCBI Gene 29107]
- **Proteins:** NXF1 (nuclear RNA export factor 1), XPO1 (exportin 1), MTR10 (mRNA transport regulator MTR10), CSE1L (chromosome segregation 1 like), USP6 (ubiquitin specific peptidase 6), NAB2 (NGFI-A binding protein 2), NXT1 (nuclear transport factor 2 like export factor 1)
- **Species:** Saccharomyces cerevisiae (taxon 4932)

## Full-text entities

- **Genes:** RRP6 (exosome nuclease subunit RRP6) [NCBI Gene 854162], NOP10 (snoRNP complex protein NOP10) [NCBI Gene 856471], NRD1 (Nrd1 complex RNA-binding subunit) [NCBI Gene 855470], SNR5 (ncRNA) [NCBI Gene 9164980], AIR1 (TRAMP complex RNA-binding subunit) [NCBI Gene 854731], CBF5 (pseudouridine synthase CBF5) [NCBI Gene 850872], TLC1 (ncRNA) [NCBI Gene 9164870], ZWF1 (glucose-6-phosphate dehydrogenase) [NCBI Gene 855480] {aka MET19, POS10}, NAB2 (mRNA-binding protein NAB2) [NCBI Gene 852755], AIR2 (TRAMP complex RNA-binding subunit) [NCBI Gene 851379], GBP2 (single-stranded telomeric DNA-binding/mRNA-binding protein) [NCBI Gene 850346] {aka RLF6}, LSM8 (U4/U6-U5 snRNP complex subunit LSM8) [NCBI Gene 853479], SNR68 (ncRNA) [NCBI Gene 9164907], NOP1 (rRNA methyltransferase NOP1) [NCBI Gene 851548] {aka LOT3}, SNU13 (RNA binding protein SNU13) [NCBI Gene 856687], RNT1 (ribonuclease III) [NCBI Gene 855280], HRP1 (Hrp1p) [NCBI Gene 853997] {aka NAB4, NAB5}, NPL3 (mRNA-binding protein NPL3) [NCBI Gene 852042] {aka MTR13, MTS1, NAB1, NOP3}, NAB3 (Nab3p) [NCBI Gene 855911] {aka HMD1}, NOP58 (RNA-processing protein NOP58) [NCBI Gene 854487] {aka NOP5}, SNR65 (ncRNA) [NCBI Gene 9164872], HEM15 (ferrochelatase HEM15) [NCBI Gene 854347], NOP56 (snoRNP complex protein NOP56) [NCBI Gene 850894] {aka SIK1}, MTR2 (Mtr2p) [NCBI Gene 853649], CRM1 (exportin CRM1) [NCBI Gene 853133] {aka KAP124, XPO1}, 21S_RRNA (21S ribosomal RNA) [NCBI Gene 9164988], SNR17A (ncRNA) [NCBI Gene 9164981], CSE1 (importin-alpha export receptor) [NCBI Gene 852612] {aka KAP109}, PAP2 (non-canonical poly(A) polymerase PAP2) [NCBI Gene 854034] {aka TRF4}, GAR1 (H/ACA snoRNP pseudouridylase subunit GAR1) [NCBI Gene 856489], CFT2 (cleavage polyadenylation factor subunit CFT2) [NCBI Gene 850806] {aka YDH1}, MEX67 (Mex67p) [NCBI Gene 855934], SNR52 (ncRNA) [NCBI Gene 9164886], PAP1 (polynucleotide adenylyltransferase PAP1) [NCBI Gene 853871], TGS1 (RNA methyltransferase) [NCBI Gene 855946], SNR24 (ncRNA) [NCBI Gene 9164952], MTR4 (ATP-dependent RNA helicase MTR4) [NCBI Gene 853397] {aka DOB1}, TRS31 (TRAPP subunit TRS31) [NCBI Gene 852083], TRF5 (non-canonical poly(A) polymerase TRF5) [NCBI Gene 855417], RNA14 (cleavage polyadenylation factor subunit RNA14) [NCBI Gene 855083], SNR13 (ncRNA) [NCBI Gene 9164878], AICDA (activation induced cytidine deaminase) [NCBI Gene 57379] {aka AID, ARP2, CDA2, HEL-S-284, HIGM2}, INTS1 (integrator complex subunit 1) [NCBI Gene 26173] {aka INT1, NDCAGF, NET28}, ACO1 (aconitate hydratase ACO1) [NCBI Gene 851013] {aka GLU1}, HRB1 (mRNA-binding protein) [NCBI Gene 855728] {aka TOM34}, SEN1 (DNA/RNA helicase SEN1) [NCBI Gene 851150] {aka CIK3, NRD2}, RAT1 (ssRNA exonuclease RAT1) [NCBI Gene 854213] {aka HKE1, TAP1, XRN2}, SKI2 (SKI complex RNA helicase subunit SKI2) [NCBI Gene 851114], NHP2 (snoRNA-binding protein NHP2) [NCBI Gene 851319], MTR10 (mRNA transport regulator MTR10) [NCBI Gene 854331] {aka KAP111}, LHP1 (tRNA maturation protein LHP1) [NCBI Gene 851509] {aka LAH1, YLA1}, YRA1 (RNA-binding protein YRA1) [NCBI Gene 851988] {aka SHE11}, ACT1 (actin) [NCBI Gene 850504] {aka ABY1, END7}
- **Diseases:** CPF-CF (MESH:D003550), cancer (MESH:D009369)
- **Chemicals:** Chloroform (MESH:D002725), agarose (MESH:D012685), xylene cyanol (MESH:C048951), CO2 (MESH:D002245), formaldehyde (MESH:D005557), Ribose (MESH:D012266), DAPI (MESH:C007293), ddNTP (MESH:D054306), Poly(A) (MESH:D011061), KCl (MESH:D011189), sodium acetate (MESH:D019346), Tween-20 (MESH:D011136), PBS (MESH:D007854), heparin (MESH:D006493), 32P (MESH:C000615311), A (MESH:D001151), sodium citrate (MESH:D000077559), formamide (MESH:C031066), glycerol (MESH:D005990), penicillin (MESH:D010406), HEPES (MESH:D006531), acetic anhydride (MESH:C031800), LiAc (-), urea (MESH:D014508), glycogen (MESH:D006003), TRIzol (MESH:C411644), sorbitol (MESH:D013012), water (MESH:D014867), triethanolamine (MESH:C009546), ethanol (MESH:D000431), 2,2,7-trimethylguanosine (MESH:C017778), oligo( (MESH:D009841), DTT (MESH:D004229), SDS (MESH:D012967), P (MESH:D010758), phosphate (MESH:D010710), MgCl2 (MESH:D015636), adenosines (MESH:D000241), NaCl (MESH:D012965), Triton X-100 (MESH:D017830), agar (MESH:D000362), streptomycin (MESH:D013307), polyacrylamide (MESH:C016679), FITC (MESH:D016650), EDTA (MESH:D004492), bromophenol blue (MESH:D001978)
- **Species:** Homo sapiens (human, species) [taxon 9606], Escherichia coli (E. coli, species) [taxon 562], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932]
- **Cell lines:** cft2-1 — Rattus norvegicus (Rat), Adenocarcinoma of the rat prostate, Cancer cell line (CVCL_3569), cdc28-13 — Oryctolagus cuniculus (Rabbit), Transformed cell line (CVCL_6E94), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12976264/full.md

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Source: https://tomesphere.com/paper/PMC12976264