XRN1 couples RNA granule remodelling to global mRNA decay triggered by the activity of a viral…

Abstract

Cytoplasmic mRNA turnover is a fundamental determinant of gene expression, yet the spatial organisation of RNA decay remains unresolved. Although decay factors are enriched in processing (P)-bodies, whether these condensates actively mediate mRNA degradation or serve primarily as storage compartments remains controversial. Here, we exploit the alphaherpesvirus endoribonuclease, virion host shutoff (vhs), to synchronously trigger rapid, global cytoplasmic mRNA accompanied by nuclear relocalisation of the poly(A)-binding protein PABPC1. Expression of vhs caused the dispersal of P-bodies, but when the 5' to 3' exonuclease XRN1 was depleted, PABPC1 remained in the cytoplasm, and P-bodies stayed intact, associating with previously undetected G3BP1-dependent RNA granules. Similarly, catalytically inactive vhs failed to disperse P-bodies but instead induced RNA granules that also contained vhs itself and recruited decay factors in an XRN1-dependent manner. Translational shutoff by this endoribonuclease did not require RNA cleavage, G3BP1 condensation or XRN1 activity supporting a sequential model in which translational arrest precedes endonucleolytic cleavage, promoting transient RNA granules that engage P-bodies and XRN1-dependent machinery for rapid mRNA degradation within the granules, thereby precluding the biogenesis of deleterious RNA condensates.

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BibTeX

@misc{elliott2026xrn1,
  title = {{XRN1 couples RNA granule remodelling to global mRNA decay triggered by the activity of a viral endoribonuclease}},
  author = {G. Elliott and A. Tweedie and C. S. Möller-Levet and B. Towler},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.03.763857},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.03.763857v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - XRN1 couples RNA granule remodelling to global mRNA decay triggered by the activity of a viral endoribonuclease
AU  - G. Elliott
AU  - A. Tweedie
AU  - C. S. Möller-Levet
AU  - B. Towler
PY  - 2026
DA  - 2026/11/03
PB  - bioRxiv
DO  - 10.64898/2026.11.03.763857
UR  - https://www.biorxiv.org/content/10.64898/2026.11.03.763857v1
AB  - Cytoplasmic mRNA turnover is a fundamental determinant of gene expression, yet the spatial organisation of RNA decay remains unresolved. Although decay factors are enriched in processing (P)-bodies, whether these condensates actively mediate mRNA degradation or serve primarily as storage compartments remains controversial. Here, we exploit the alphaherpesvirus endoribonuclease, virion host shutoff (vhs), to synchronously trigger rapid, global cytoplasmic mRNA accompanied by nuclear relocalisation of the poly(A)-binding protein PABPC1. Expression of vhs caused the dispersal of P-bodies, but when the 5' to 3' exonuclease XRN1 was depleted, PABPC1 remained in the cytoplasm, and P-bodies stayed intact, associating with previously undetected G3BP1-dependent RNA granules. Similarly, catalytically inactive vhs failed to disperse P-bodies but instead induced RNA granules that also contained vhs itself and recruited decay factors in an XRN1-dependent manner. Translational shutoff by this endoribonuclease did not require RNA cleavage, G3BP1 condensation or XRN1 activity supporting a sequential model in which translational arrest precedes endonucleolytic cleavage, promoting transient RNA granules that engage P-bodies and XRN1-dependent machinery for rapid mRNA degradation within the granules, thereby precluding the biogenesis of deleterious RNA condensates.
ER  -

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