# Assembly of the eukaryotic small ribosomal subunit

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2022 · $339,000

## Abstract

Project Summary
Ribosomes are molecular machines composed of ribosomal RNAs and up to 80 ribosomal proteins.
These large assemblies catalyze protein synthesis in all cells. The long-term goal of this project is to
understand how eukaryotic ribosomes are assembled with the help of more than 200 non-ribosomal
factors as a series of molecular snapshots of assembly intermediates. Combining genetic, biochemical
and mass spectrometry approaches with cryo-EM is an essential step to engineer, trap, isolate and
determine atomic-resolution molecular snapshots of transient assembly intermediates of ribosomal
subunits.
Eukaryotic ribosome assembly can be subdivided into four stages, co-transcriptional assembly events
and initial maturation of small and large ribosomal subunit precursors in the nucleolus, nuclear
maturation of pre-40S and pre-60S particles, nuclear export, and cytoplasmic maturation. While late
events in eukaryotic ribosome assembly are relatively well characterized, the early assembly of
ribosomal subunits in the nucleolus is still poorly understood. Especially the mechanisms responsible
for early human small ribosomal subunit assembly have remained elusive due to a biomolecular
condensate that retains these early particles in human nucleoli.
This proposal describes new approaches to define the molecular mechanisms that govern nucleolar
maturation of the eukaryotic small ribosomal subunit. My laboratory has developed new human genome
editing and biochemical approaches that now enable us to efficiently tag and isolate early nucleolar
assembly intermediates of the human small ribosomal subunit. The synergistic use of these approaches
has allowed us to overcome previously intractable biochemical hurdles, thereby enabling the detailed
study of essential early assembly intermediates of the small ribosomal subunit.
Insights from these studies will shed light onto both the mechanisms that are employed during
eukaryotic ribosome assembly to coordinate key processing events as well as how defects in eukaryotic
ribosome assembly can result in human blood disorders, which are collectively termed
ribosomopathies.

## Key facts

- **NIH application ID:** 10421870
- **Project number:** 1R01GM145950-01
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Sebastian Klinge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $339,000
- **Award type:** 1
- **Project period:** 2022-04-20 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10421870

## Citation

> US National Institutes of Health, RePORTER application 10421870, Assembly of the eukaryotic small ribosomal subunit (1R01GM145950-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10421870. Licensed CC0.

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