# Mechanisms of environmentally regulated alternative splicing in S.Pombe

> **NIH NIH R01** · CORNELL UNIVERSITY · 2020 · $321,016

## Abstract

ABSTRACT
Pre-mRNA splicing is an essential component of eukaryotic gene expression. Many metazoans, including
humans, regulate alternative splicing patterns to generate expansions of their proteome from a limited number
of genes. Importantly, a considerable fraction of human disease causing mutations manifest themselves by
altering the sequences that shape the splicing patterns of genes. Nevertheless, the mechanisms by which this
complex pathway is regulated remain poorly understood. Understanding how disease-causing mutations impair
this ability will require improved knowledge of the mechanisms by which the spliceosome correctly identifies and
activates ‘cognate’ splice site sequences in the background of scores of ‘near-cognate’ aberrant splice sites, and
in the context of changing developmental and environmental cues. At the simplest level, this will require
understanding both: (1) the cis-regulatory elements within a transcript (or gene structure) that destine it for
regulation; and (2) the mechanistic bases by which trans-regulatory factors can impart this specific regulation.
To better understand the mechanisms of alternative pre-mRNA splicing, we have chosen to examine the
genetically tractable fission yeast, Schizosaccharomyces pombe. In many ways, splicing in S. pombe looks
similar to splicing in higher eukaryotes. Introns have been identified in nearly half of all S. pombe genes, and
single genes are interrupted by multiple introns. The splice site sequences found in S. pombe introns do not
conform to tight consensus sequences but rather appear much more like human introns in the nucleotide
degeneracy found at these positions, a known hallmark of splicing regulation. Building upon our recent
demonstrations that S. pombe can catalyze mammalian-like environmentally-regulated alternative splicing, the
goals of our current work are to understand the cis-regulatory elements and trans-acting factors that are
necessary for this regulation. Toward this end, we will employ high-throughput genetic tools that we have
developed to identify the elements within these transcripts that are required for their regulation. Similarly, we will
use a forward genetic approach to identify and characterize the splicing factors that are necessary for these
regulated events. The combination of these approaches should provide important insights into the mechanisms
by which this organism can regulate its gene expression via this pathway. Given the high level of conservation
between splicing in S. pombe and humans, this work is likely to provide critical insights into splicing regulation
in higher eukaryotes, including its mis-regulation in many human diseases.

## Key facts

- **NIH application ID:** 9979939
- **Project number:** 5R01GM098634-09
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** JEFFREY A PLEISS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,016
- **Award type:** 5
- **Project period:** 2011-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979939

## Citation

> US National Institutes of Health, RePORTER application 9979939, Mechanisms of environmentally regulated alternative splicing in S.Pombe (5R01GM098634-09). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/9979939. Licensed CC0.

---

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