# Genomic Analysis of Nucleic Acid Transactions

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $75,100

## Abstract

Project Summary (as submitted in original application)
 Most eukaryotic pre-mRNAs, especially in metazoans, are alternatively spliced to
generate multiple mRNAs and proteins. Given the importance of alternative splicing in regulating
gene expression and enhancing the diversity of the proteome, it is essential to understand the
mechanisms of splicing and how alternative splicing is regulated. In this project, we will study
the roles of RNA binding proteins in alternative splicing, with an emphasis on how RNA binding
proteins auto- and cross-regulate the splicing their own and other RNA binding protein genes.
This work will provide new insight into the mechanisms of RNA processing and how these
proteins regulate one another to achieve homoestasis.
 Many prokaryotes encode CRISPR-Cas systems which are RNA-guided adaptive
immune systems that protects prokaryotic organisms against invaders such as viruses and
plasmids. Immune memories are encoded as short DNA sequences, called “spacers”, that
match invader genomes and are stored as interspersed elements in an array of short repeats
(the CRISPR array). The CRISPR arrays are transcribed and processed into guide RNAs which
pair with Cas nucleases to recognize and degrade target nucleic acid (interference). New
immune memories are formed during “adaptation” when fragments of invader DNA are acquired
and integrated into CRISPR arrays for use in future targeting. While a tremendous amount is
known about the targeting and degradation of invading nucleic acids, much less is known about
the process of adaptation. We plan to further characterize the adaptation process in prokaryotic
CRISPR-Cas systems. This work will also provide insight into the mechanisms of adaptation in
the immune systems of prokaryotes. In addition to enhancing our understanding of the basic
science of prokaryotic immune systems, there is tremendous potential that this work could lead
to the development of new tools that can be used for genome editing applications.
 All of these projects will be addressed using the types of general approaches we have
developed such as splicing reporters, single cell RNA-Seq, nanopore sequencing, RNAi or
CRISPR screens, and computational genomics. We will also continue to develop additional
innovative approaches to address these issues as needed or as opportunities arise due to
technical advances in the field.

## Key facts

- **NIH application ID:** 10389453
- **Project number:** 3R35GM118140-06S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Brenton R. Graveley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,100
- **Award type:** 3
- **Project period:** 2016-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389453

## Citation

> US National Institutes of Health, RePORTER application 10389453, Genomic Analysis of Nucleic Acid Transactions (3R35GM118140-06S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10389453. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*