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

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $440,503

## Abstract

Project Summary/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:** 9856451
- **Project number:** 5R01GM105681-06
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** William G Fairbrother
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,503
- **Award type:** 5
- **Project period:** 2014-07-16 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856451

## Citation

> US National Institutes of Health, RePORTER application 9856451, A genomic approach to studying the life cycle of intron lariats (5R01GM105681-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856451. Licensed CC0.

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