# Building Knowledge About Alternatively-spliced Dual-Coding Exons

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2023 · $191,875

## Abstract

Abstract
Most protein-coding genes in humans and other eukaryotes are made up of a collection of exons,
which are concatenated to form the messenger RNA (mRNA) that encodes a final protein
product. The well-known phenomenon of alternative splicing makes it possible for a single gene
to encode multiple protein products, by conditionally including only a subset of the gene’s exons
into the expressed mRNA. A more surprising mechanism for producing alternate protein products
is to utilize an alternate reading frame of a standard exon, through aberrant splicing; using
custom software built in our research group, we have found that this mechanism appears to be
quite common. Specifically, ~13% of all human genes include at least one exon that conditionally
encodes alternate peptides, and these “dual-coding exons” are highly-conserved: 98%
correspond to homologous exons in the mouse genome that also encode two open reading
frames. Light exploration has identified dozens of human genes that show tissue-specific
patterns of reading frame usage, suggesting a functional role for at least some of these variants.
Here, we describe a plan to (i) leverage massive public atlases of human tissue-specific and
development-specific RNA-Seq and mass spectrometry data to tabulate the extent of differential
use of these frame-shifted splicing variants, and to (ii) analyze the computationally-predicted
structural and functional impact of dual-coding variants, and the sequence signals controlling
them. The results of these analyses will be accumulated for release in an open and accessible
web service.

## Key facts

- **NIH application ID:** 10701663
- **Project number:** 5R21HG012283-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Travis John Wheeler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $191,875
- **Award type:** 5
- **Project period:** 2022-09-09 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701663

## Citation

> US National Institutes of Health, RePORTER application 10701663, Building Knowledge About Alternatively-spliced Dual-Coding Exons (5R21HG012283-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10701663. Licensed CC0.

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