# Regulation of Ribosome Biogenesis

> **NIH NIH R35** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $412,500

## Abstract

Abstract
Ribosomes are among the most ancient, intricate, and essential cellular machines whose function is to process
genetic information to generate cellular proteins. Human ribosomes are incredibly complex, consisting of 80
ribosomal proteins and four heavily modified ribosomal RNAs (rRNA), which must be precisely assembled.
Further, the largest pre-rRNA is transcribed from a polycistronic gene repeated more than 300 times in the
genome. This pre-rRNA must be post-transcriptionally processed to remove external and internal spacers to
release mature rRNAs. The majority of these assembly events occur in a specialized nuclear body called the
nucleolus. Owing, in part, to their complex assembly process, it is now appreciated that not all ribosomes are
the same, and it has been suggested that heterogenous ribosomes may have specialized functions. We have
discovered that an undetermined stress response pathway regulates early events in rRNA processing. We have
shown that this pathway is activated by oxidative stress, select viral infections, and chemotherapeutic drugs.
Activation results in unprocessed pre-rRNA being stored in the nucleolus, which re-enters the maturation process
when stress resolves. We are undertaking a multi-omics approach to uncover this pathway and determine how
this prolonged stalling of processing and storage of pre-rRNA in the nucleolus affects the assembly and activity
of ribosomes generated in this time window. We have developed a novel technique that allows for the time-
resolved capture of ribosomes to address this question. Further, analysis of processing sites demonstrates
profound sequence heterogeneity across the different repeated genes through the genome, raising the possibility
that processing events are differentially regulated between rRNA genes. We expect to clarify the sequence motifs
required for early rRNA processing and determine how naturally occurring variants contribute to the differential
expression of sub-types of ribosomes. We seek to understand better the basic principles governing ribosome
biogenesis in light of diverse sequence variation and how various stimuli alter the process of ribosome assembly.

## Key facts

- **NIH application ID:** 10906205
- **Project number:** 5R35GM146769-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Shawn M Lyons
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906205

## Citation

> US National Institutes of Health, RePORTER application 10906205, Regulation of Ribosome Biogenesis (5R35GM146769-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10906205. Licensed CC0.

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