# Dissecting the Mechanisms of Regulation and Quality Control in Ribosome Assembly and the Consequences of their Failure

> **NIH NIH R35** · SCRIPPS FLORIDA · 2020 · $868,507

## Abstract

PROJECT SUMMARY
Ribosomes carry out protein synthesis in all cells, interpreting the information contained in the mRNA to
produce the proper amount of the correct protein. In addition, ribosomes also mediate mRNA quality control.
Thus, misassembled ribosomes can affect the sequence and abundance of proteins and mRNAs, thereby
disrupting protein homeostasis. This can lead to a number of diseases, demonstrating the importance of
ensuring ribosomes are accurately assembled, and produced in the correct numbers.
Using a combination of biochemical, genetic, genomic and structural tools, we will (i) investigate mechanisms
that promote proper incorporation of ribosomal proteins and folding of the RNA, (ii) dissect quality control
pathways to identify and ultimately degrade misassembled intermediates and (iii) study how misassembled
ribosomes promote disease.
In the first part, we will build on our existing work and study the late assembly of the ribosomal head, as well
as combine insights from recent structures and our biochemical work to understand how DEAD-box proteins
are used to construct ATP-dependent regulatory switches to control major conformational transitions in early
40S biogenesis.
In the second part, we will extend our work on quality control to investigate a possible proofreading
mechanism and identify degradation pathways for misassembled intermediates, a novel frontier for the field.
In the last part, we will investigate how ribosomes containing substoichiometric levels of two ribosomal
proteins, Asc1 and Rps10, which are produced in cancer cells that lack sufficient amounts of the assembly
factor Ltv1, promote disease. This work builds on a genetic system we have developed to separate ribosomes
of distinct composition, and also takes into consideration the known roles of these proteins in mRNA quality
control. In addition, we will also investigate the effects from dysregulation of ribosome numbers in disease.
Together, the proposed work will link mechanistic insights into a fundamental problem of cell and molecular
biology – how ribosomes are assembled, to human disease.

## Key facts

- **NIH application ID:** 9930946
- **Project number:** 1R35GM136323-01
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Katrin Karbstein
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $868,507
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930946

## Citation

> US National Institutes of Health, RePORTER application 9930946, Dissecting the Mechanisms of Regulation and Quality Control in Ribosome Assembly and the Consequences of their Failure (1R35GM136323-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9930946. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*