# RNA and Genomic Junk in Fundamental Chromosome Architecture and Regulation

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $598,444

## Abstract

ABSTRACT
The central mystery that drives our research is how thousands of genes are coordinately regulated during
development to provide orchestrated expression programs that define specific cell-types. We hypothesize that
this involves establishing stable patterns of heterochromatin and euchromatin which are, in part, controlled at
the level of chromosomal domain and nuclear organization. For this MIRA application, we have worked to
conceptually integrate research projects which address complementary aspects of our overall vision, focusing
on a theme around the role of non-coding RNAs in chromatin regulation. We continue to contribute to the
fascinating biology of XIST RNA, which controls inactivation of one X-chromosome in female cells. However,
findings over several years motivate our increasing emphasis on the role of repeat-rich “junk” of the genome,
the main component of chromosomes. In our view, this part of our genomes is dramatically understudied
relative to its potential contribution to the biology and regulation of chromosomes. Based on strong preliminary
results, we hypothesize that repeat-rich elements play a role at the DNA level in chromosome architecture, and
at the RNA level in regulation of that architecture. Rather than RNA as an occasional modifier of chromatin,
our results support that RNA with chromosome structure is more the rule than the exception. In fact, we will
investigate whether ubiquitous RNAs are essential to maintaining decondensed and condensed chromatin
structure in nuclei. Our preliminary RNAseq analysis supports that long-lived “junk” RNAs are structurally
embedded in nuclear structure. In fact, our work is likely to show that, rather than RNA being tethered to
chromatin by a scaffold protein, as currently believed, many architectural and regulatory proteins are actually
tethered by RNA. This work is supported by a team of collaborators who are leaders in different aspects of
RNA, chromatin and computational biology, and who are enthused to work with us on these compelling,
potentially paradigm shifting ideas. Although this work is largely of a fundamental nature, aspects of our
studies have direct relevance to the translation of this knowledge to the common problem of chromosomal
trisomy.

## Key facts

- **NIH application ID:** 9933059
- **Project number:** 5R35GM122597-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** JEANNE Bentley LAWRENCE
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $598,444
- **Award type:** 5
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933059

## Citation

> US National Institutes of Health, RePORTER application 9933059, RNA and Genomic Junk in Fundamental Chromosome Architecture and Regulation (5R35GM122597-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9933059. Licensed CC0.

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