# Genomic Analysis of Nucleic Acid Transactions

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2023 · $632,427

## Abstract

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:** 10596116
- **Project number:** 5R35GM118140-08
- **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:** 2023
- **Award amount:** $632,427
- **Award type:** 5
- **Project period:** 2016-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596116

## Citation

> US National Institutes of Health, RePORTER application 10596116, Genomic Analysis of Nucleic Acid Transactions (5R35GM118140-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10596116. Licensed CC0.

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