# Regulation of Ribosome Biogenesis During Stress

> **NIH NIH R00** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $236,000

## Abstract

Abstract
The integrated stress response (ISR) reprograms cellular gene expression to promote survival until transient
stresses have passed. A major aim of the ISR is to redirect cellular energy reserves from pro-growth pathways
towards pro-survival pathways. As biogenesis of ribosomes is an incredibly energy intensive task and mass
production of new ribosomes are most needed during growth, it is not surprising that ribosome biogenesis is
regulated during stress. However, how this regulation is accomplished and how it is intertwined with the ISR is
unknown. Ribosomes are composed of 4 non-coding RNAs (rRNAs) and 80 ribosomal proteins (RPs). Proper
coordination of rRNA and RP synthesis is critical to cellular homeostasis. Therefore, the ISR must co-regulate
rRNA and RP synthesis during cellular stress. Failure to do so would only further compound the cellular insult.
Data presented here identifies angiogenin (ANG) as a major regulator of ribosome biogenesis during ISR. We
previously identified ANG as the protein that cleaves tRNAs during ISR to produce a set of novel small RNAs
called tRNA-derived stress-induced RNAs (tiRNAs). We have shown that tiRNAs inhibit translation during a
stress response and that Y-box binding protein 1 (YB1) is involved in this pathway. Data presented here shows
that a 2nd protein, cellular nucleic acid binding protein (CNBP), is also a component of this pathway. We also
show that during a stress response, tiRNAs specifically regulate the translation of RPs. Further, we
demonstrate that YB1 has a role in RP biosynthesis. Finally, in unstressed cells, ANG promotes the expression
of rRNA via an unknown mechanism. Data presented here suggests that ANG is an rRNA processing enzyme
and, upon activation of the ISR, rRNA processing is inhibited. This allows for co-regulation of RP and rRNA
synthesis. This proposal will study 1) How tiRNAs specifically regulate RP translation under stress, 2)
Determine the role that YB1 plays in ribosome biogenesis and 3) Show how rRNA processing is regulated
under stress and determine the role ANG plays in this process.

## Key facts

- **NIH application ID:** 10076909
- **Project number:** 4R00GM124458-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Shawn M Lyons
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $236,000
- **Award type:** 4N
- **Project period:** 2018-09-13 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076909

## Citation

> US National Institutes of Health, RePORTER application 10076909, Regulation of Ribosome Biogenesis During Stress (4R00GM124458-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076909. Licensed CC0.

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