# A genomic approach to studying the life cycle of intron lariats

> **NIH NIH R01** · BROWN UNIVERSITY · 2021 · $25,279

## Abstract

Pre-mRNA splicing is a critical and regulated processing event where introns are 
precisely excised from nascent RNA transcripts. As many as one third of all heritable disease 
mutations result in splicing defects. This research studies the role of branchpoints in 
determining splice site selection (3'ss) is utilized in vivo and also the effect branchpoints have 
on the life cycle of the intron. Each pre-mRNA splicing event creates a lariat and spliced exon 
junction. While a great deal is known about splice exon junctions almost nothing is known 
 about lariats. By mapping all branchpoints in the human genome, we are opening up a 
whole new area of analysis. The identification of branchpoints by transcript data will 
facilitate the interpretation of clinical sequencing data. In addition to the intrinsic value of 
this data, the successful completion of this proposal will test some hypothesis about the 
fundamental catalysis and recognition that occurs in vivo in the processing of eukaryotic genes. 
Studying these intermediates at a system wide level will bring a biochemical-level understanding to 
hundreds of thousands of processing events. Furthermore, each intron lariat has a lifecycle - 
created by splicing of a transcribed product, recycled by debranching and degradation. The 
recycling of introns is vital to replenishing the intracellular levels of free nucleotides and 
to return splicing factors into active spliceosomes. Some introns have a second life after splicing 
as non-coding RNAs (ncRNAs). As we are sampling steady state levels of introns we gain insight 
into both these processes. This proposal seeks to follow this lead by exploring some of the reasons 
why certain introns appear stabilized.

## Key facts

- **NIH application ID:** 10251555
- **Project number:** 3R01GM105681-06S1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** William G Fairbrother
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $25,279
- **Award type:** 3
- **Project period:** 2014-07-16 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251555

## Citation

> US National Institutes of Health, RePORTER application 10251555, A genomic approach to studying the life cycle of intron lariats (3R01GM105681-06S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10251555. Licensed CC0.

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