Single-Cell Inference of Structural States Of Ribosomes
- 1Oncode Institute, Hubrecht Institute - KNAW and University Medical Center Utrecht, Utrecht, the Netherlands
Abstract
Protein synthesis is dynamically regulated to control cell growth, differentiation, and stress responses. Recent single-cell sequencing methods can map ribosome positions on individual transcripts, but cannot capture the global translational states that coordinate protein synthesis across the transcriptome. In contrast, methods that measure the global translational landscape, such as polysome profiling and cryogenic electron tomography, lack either single-cell resolution or throughput. Here we introduce SCISSOR (Single-Cell Inference of Structural States of Ribosomes), a strategy that infers global translation activity in individual cells from the differential protection of ribosomal RNA (rRNA) against nuclease digestion. By integrating these protection signatures with the structure of the ribosome, SCISSOR resolves multiple ribosomal states and quantifies their abundance across thousands of individual cells. Applying SCISSOR reveals systematic variation in global translation across the cell cycle in human cells, as well as during the differentiation of murine intestinal stem cells into distinct epithelial lineages. These findings uncover principles of global translational regulation that are invisible to transcriptomic or ribosome-profiling assays, establishing a framework for studying global translation control at single-cell resolution.
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BibTeX
@misc{jolysmith2026singlecell,
title = {{Single-Cell Inference of Structural States Of Ribosomes}},
author = {E. Joly-Smith and M. VanInsberghe and K. Sarieva and E. Marinelli and R. M. van Es and P. Sobrevals Alcaraz and H. R. Vos and A. Andersson-Rolf and H. Clevers and A. van Oudenaarden},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.29.747780},
url = {https://www.biorxiv.org/content/10.64898/2026.08.29.747780v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Single-Cell Inference of Structural States Of Ribosomes
AU - E. Joly-Smith
AU - M. VanInsberghe
AU - K. Sarieva
AU - E. Marinelli
AU - R. M. van Es
AU - P. Sobrevals Alcaraz
AU - H. R. Vos
AU - A. Andersson-Rolf
AU - H. Clevers
AU - A. van Oudenaarden
PY - 2026
DA - 2026/08/29
PB - bioRxiv
DO - 10.64898/2026.08.29.747780
UR - https://www.biorxiv.org/content/10.64898/2026.08.29.747780v1
AB - Protein synthesis is dynamically regulated to control cell growth, differentiation, and stress responses. Recent single-cell sequencing methods can map ribosome positions on individual transcripts, but cannot capture the global translational states that coordinate protein synthesis across the transcriptome. In contrast, methods that measure the global translational landscape, such as polysome profiling and cryogenic electron tomography, lack either single-cell resolution or throughput. Here we introduce SCISSOR (Single-Cell Inference of Structural States of Ribosomes), a strategy that infers global translation activity in individual cells from the differential protection of ribosomal RNA (rRNA) against nuclease digestion. By integrating these protection signatures with the structure of the ribosome, SCISSOR resolves multiple ribosomal states and quantifies their abundance across thousands of individual cells. Applying SCISSOR reveals systematic variation in global translation across the cell cycle in human cells, as well as during the differentiation of murine intestinal stem cells into distinct epithelial lineages. These findings uncover principles of global translational regulation that are invisible to transcriptomic or ribosome-profiling assays, establishing a framework for studying global translation control at single-cell resolution.
ER -