40S Ribosome Remodeling Triggers 18S rRNA U-tailing and DIS3L2-dependent Decay
- 1National Cancer Institute
Abstract
Eliminating defective ribosomes through quality control is essential for accurate protein synthesis. However, the mechanisms that commit ribosomal subunits to decay remain poorly defined. Here, we identify a tandem mechanism in which ubiquitin-mediated ribosome remodeling and 18S rRNA uridylation lead to 40S ribosomal subunit decay. Specifically, we use an in vitro reconstitution system to show that the atypical kinase RIOK3 displaces the ribosomal protein eS26 from 40S subunits, exposing the 3 end of 18S rRNA. Nanopore direct RNA sequencing and motif analyses reveal that this remodeling event promotes oligo-uridylation, generating uridylated 18S rRNA decay intermediates. We further show that this uridylated 18S rRNA is selectively degraded by the 3-5 exoribonuclease DIS3L2. Moreover, DIS3L2-mediated exoribonucleolytic cleavage triggers endoribonucleolytic decay of the 18S rRNA, amplifying turnover. Together, our findings define a stepwise mechanism in which ribosome remodeling and RNA tailing commit defective 40S subunits to elimination, establishing a mechanistic framework for ribosome surveillance in mammalian cells.
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BibTeX
@misc{shah2026ribosome,
title = {{40S Ribosome Remodeling Triggers 18S rRNA U-tailing and DIS3L2-dependent Decay}},
author = {A. Shah and A. R. Coria and J. T. Miller and E. Orgebin and W. Guiblet and A. Yang and S. Gu and C. Wu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.750429},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.750429v1},
note = {CC0},
}
RIS
TY - UNPB
TI - 40S Ribosome Remodeling Triggers 18S rRNA U-tailing and DIS3L2-dependent Decay
AU - A. Shah
AU - A. R. Coria
AU - J. T. Miller
AU - E. Orgebin
AU - W. Guiblet
AU - A. Yang
AU - S. Gu
AU - C. Wu
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.750429
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.750429v1
AB - Eliminating defective ribosomes through quality control is essential for accurate protein synthesis. However, the mechanisms that commit ribosomal subunits to decay remain poorly defined. Here, we identify a tandem mechanism in which ubiquitin-mediated ribosome remodeling and 18S rRNA uridylation lead to 40S ribosomal subunit decay. Specifically, we use an in vitro reconstitution system to show that the atypical kinase RIOK3 displaces the ribosomal protein eS26 from 40S subunits, exposing the 3 end of 18S rRNA. Nanopore direct RNA sequencing and motif analyses reveal that this remodeling event promotes oligo-uridylation, generating uridylated 18S rRNA decay intermediates. We further show that this uridylated 18S rRNA is selectively degraded by the 3-5 exoribonuclease DIS3L2. Moreover, DIS3L2-mediated exoribonucleolytic cleavage triggers endoribonucleolytic decay of the 18S rRNA, amplifying turnover. Together, our findings define a stepwise mechanism in which ribosome remodeling and RNA tailing commit defective 40S subunits to elimination, establishing a mechanistic framework for ribosome surveillance in mammalian cells.
ER -