# Monoalleleic autosomal spreading of a novel family of nucleolus-localized ncRNAs

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $234,945

## Abstract

Nucleolus is the most prominent nuclear domain (ND) and is where rRNAs (ribosomal RNAs) are
synthesized, processed and assembled with ribosomal proteins. There is growing evidence ascribing an
essential role for the nucleolus in cellular aging. Perturbations in nucleolus structure and rDNA expression
have been associated with aging related diseases such as progeria. However, the molecular mechanisms
controlling the differential expression of 300-400 rDNA genes clustered in the short arms of five human
chromosomes are yet to be determined. Recent studies indicated that nucleolus-localized noncoding RNAs
(ncRNAs) contribute to cellular aging by controlling rDNA expression under conditions that influence aging
(such as quiescence). We have now generated preliminary data showing the existence of a novel class of
nucleolus-localized ncRNA, SNULs (Single NUcleolus-Localized RNAs) that control rDNA expression.
SNULs form distinct non-overlapping ‘RNA clouds’ within the nucleolus, where they coat rDNA repeat or
nucleolus organizer regions (NOR) containing short arms (p-arm) of chromosomes. Specifically, SNULs
painted only one of the two alleles of each autosome. Further, loss of function studies revealed that SNULs
inhibit rDNA expression. The central hypothesis of the present proposal is that SNULs control rDNA
expression by regulating rDNA expression. The objectives of this proposal are to identify the determinants
underlying allele-specific chromosome coating of SNULs, and to gain insights into the involvement of
SNULs in rDNA expression. Guided by strong preliminary data, this hypothesis will be tested in the following
specific aims: 1) Determine how cells achieve allele-specific expression/coating of SNULs. 2) Determine
how SNUL family of ncRNAs regulates rDNA expression. In the first aim, PI will characterize SNULs and will
test whether SNULs display monoallelic chromosome coating utilizing imprinted mechanism or random
monoallelic association. Under the second aim, by performing loss-of-function studies, PI will determine the
involvement of SNULs in rDNA expression or nucleolar chromatin organization. Our observation of the
coating of autosomes by SNULs supports a ‘paradigm shifting’ model that ncRNA-coating of chromosomes
are not restricted only to sex chromosomes. The proposed research will be of strong biological significance
through an increased understanding of how cells restrict monoallelic spreading of ncRNAs on autosomes,
and their impact on gene expression. The approach is technically innovative, because it employs state of
the art cell biological techniques, including super-resolution imaging and genomic approaches such as
targeted iso-sequencing to annotate repeat-rich RNAs. Overall, this exploratory proposal holds a strong
chance of unraveling a previously unknown mechanism underlying autosomal coating of ncRNAs, and could
lead to deeper exploration of this phenomenon under physiological and pathological settings.

## Key facts

- **NIH application ID:** 9875040
- **Project number:** 1R21AG065748-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Prasanth Kumar Vijayan Kannanganattu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,945
- **Award type:** 1
- **Project period:** 2020-02-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875040

## Citation

> US National Institutes of Health, RePORTER application 9875040, Monoalleleic autosomal spreading of a novel family of nucleolus-localized ncRNAs (1R21AG065748-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9875040. Licensed CC0.

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