# Biochemistry of Pre-mRNA Splicing

> **NIH NIH R01** · COLD SPRING HARBOR LABORATORY · 2024 · $806,400

## Abstract

ABSTRACT
The central goal of this project is to understand fundamental mechanisms of human pre-mRNA
splicing, a required step in the expression of most eukaryotic genes, as well as the regulation of
alternative splicing. Specific mechanisms through which exons and introns are correctly identified
by the spliceosome will continue to be investigated. These studies will focus on recognition of the
canonical and non-canonical splice sites by snRNAs and RNA-binding proteins, and on contextual
effects due to other pre-mRNA features, such as splicing enhancer elements recognized by SR
proteins. The mechanisms of action and specificity of antisense-oligonucleotide and small-
molecule splicing modulators will be explored, as will the interplay between alternative splicing
and chromatin. In addition, the network of protein-protein interactions of the SR protein SRSF1
will continued to be investigated, with the goal of obtaining structural insights about its various
functions in splicing. This project will rely on integrative approaches, including molecular,
bioinformatics, biochemical, biophysical, proteomics, cell biology, and pharmacological
techniques, as well as in vitro, cell-based, and in vivo assays. In addition to obtaining new insights
into basic mechanisms of gene expression, these studies will improve the understanding of
numerous mutations associated with various genetic diseases, as well as facilitate correct genetic
diagnosis and therapeutics development for such diseases.

## Key facts

- **NIH application ID:** 10816435
- **Project number:** 5R01GM042699-33
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Adrian R Krainer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $806,400
- **Award type:** 5
- **Project period:** 1989-07-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10816435

## Citation

> US National Institutes of Health, RePORTER application 10816435, Biochemistry of Pre-mRNA Splicing (5R01GM042699-33). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10816435. Licensed CC0.

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