# Targets and functions of the mammalian snoRNAome

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $773,773

## Abstract

Project Abstract:
Small nucleolar RNA (snoRNA) are natural guide non-coding RNAs derived from over 900 annotated snoRNA
genes in the human genome. The major known function of about one-third of snoRNAs is to install 2’O-methyl
and pseudouridine modifications in the ribosomal RNA. These rRNA modifications guide ribosome assembly
and maturation, and fine-tune translation in a cell type and cell state dependent manner. However, the majority
of snoRNAs do not have a well described function; they are called orphans because their cellular RNA targets
are not known. How snoRNA interacts with the human transcriptome and the functional consequences of these
potential non-canonical snoRNA-RNA interactions in gene expression regulation and human diseases remain to
be determined. We recently developed several new sequencing technologies that are directly relevant to
studying snoRNA biology. They include methods to robustly identify inter-molecular RNA-RNA interactions in
cells and transcriptome-wide sequencing of 2’O-methyl and pseudouridine modifications. These new tools will
allow us to address mysteries of snoRNA biology. Aim 1 will identify the cellular RNA targets of the snoRNAome
through an advanced version of kethoxal-assisted RNA-RNA interaction sequencing (KARR-seq) approach to
enable comprehensive capture and identification of snoRNA-RNA interactions at the transcriptomic scale. These
results will be used to identify the rules of snoRNA-guided targeting of mRNA sequences. Aim 2 will investigate
two types of snoRNA-mRNA interactions transcriptome-wide and the consequences on regulating gene
expression through the application of new sequencing methods to map 2’O-methyl and pseudouridine
modifications in pre-mRNA and mature mRNA, and associate these results with the snoRNA-mRNA interactome.
We will also selectively delete snoRNA genes or knockdown snoRNA levels, alter the expression of snoRNP
components to investigate the consequence of specific snoRNA-mRNA interaction. All together these results will
provide the first comprehensive snoRNA-RNA interactome and derive the guiding principles of snoRNA-mRNA
interactions and the associated biological functions.

## Key facts

- **NIH application ID:** 10565187
- **Project number:** 1R01HG012780-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** CHUAN HE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $773,773
- **Award type:** 1
- **Project period:** 2022-09-22 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10565187

## Citation

> US National Institutes of Health, RePORTER application 10565187, Targets and functions of the mammalian snoRNAome (1R01HG012780-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10565187. Licensed CC0.

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