# Long noncoding RNA expressing genomic element that control antibody diversification and chromosomal integrity in B cells

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $479,432

## Abstract

PROJECT SUMMARY/ ABSTRACT
It is becoming increasingly evident that the majority of the mammalian genome has the potential to
express non-coding RNAs (ncRNAs). However, the functionality and mechanism(s) of regulation of
these ncRNAs are just beginning to be explored. One challenge that biologists encounter is the
detection of these ncRNAs, which often tend to be transcriptionally tightly controlled and rapidly
degraded. We have recently identified a long noncoding (lnc) RNA expressing locus, known as
lncRNA-CSR, that regulates DNA rearrangments in the Immunoglobulin heavy chain (IgH) locus of B
cells. Using mouse model systems that lack lncRNA processing/degradation activity along with a
combination with high throughput genomics, bioinformatics, and various ChIP-seq based
experiments, we are able to predict long-range transcription enhancer function of the lncRNA-CSR
locus. In this application, we continue to focus our investigation on the functionality of lncRNA-CSR
and three other novel lncRNA expressing loci, that we propose to have a role in orchestrating DNA
rearrangment events in germinal center resident B cells. B lymphocytes have the unique ability to
undergo programmed somatic mutagenesis of their genomes (at immunoglobulin gene loci) to
generate the diversity of antibodies required by our immune system to combat the plethora of
antigens we might encounter, a process known as antibody diversification. However, as collateral
damage emerging from this very unusual and useful ability to undertake beneficial somatic
mutagenesis events is the ability of B cells accidently to mutate their genome at a very low frequency
at various inappropriate locations. These accidental mutations are the cause of various B cell
malignancies, particularly those that evolve from germinal center derived B cells. Interestingly,
cancer-causing translocations in B cells occur at regions of divergent transcription—that is, promoters
and enhancers—which exist inside topological domains of superenhancer clusters. We postulate that
lncRNA-CSR is responsible for tethering long distant regulatory elements (i.e, promoters and
enhancers) in the IgH locus superenhancer cluster to facilitate genome organization, transcription
control of regulated genes, and, ultimately, to promote antibody diversification mechanisms without
inducing cancer causing DNA alterations.

## Key facts

- **NIH application ID:** 10065485
- **Project number:** 5R01AI134988-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Uttiya Basu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,432
- **Award type:** 5
- **Project period:** 2017-12-07 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065485

## Citation

> US National Institutes of Health, RePORTER application 10065485, Long noncoding RNA expressing genomic element that control antibody diversification and chromosomal integrity in B cells (5R01AI134988-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10065485. Licensed CC0.

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