# Discovery and Characterization of sORFs encoding mitochondrial peptides with a Role in Heart Failure

> **NIH NIH F31** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $25,391

## Abstract

Project Summary
The advent of genomic sequencing revolutionized the field of science, revealing the human genome sequence
to be ~3 billion base pairs. The result of this venture was the identification of ~20,000 protein-coding genes,
which compromise only ~1% of the genome. While ~10% of the genome is considered ‘silent’, the remaining
~89% is transcribed, but thought to be untranslated. Previous annotation methods resulted in the exclusion of
transcripts under 300bp (100aa) due to the high rate of gene misidentification. Recent papers have discovered
small open reading frames (sORFs) that encode peptides under 100aa with distinct biological functions. We
hypothesize that there are numerous peptides with unknown biological functions that are prominent in cardiac
physiology and disease. To identify novel sORFs we combined in vivo and in silico approaches, including a
statistical prediction algorithm sORfinder, to compile a database of putative sORFs. Given the prominent role
of mitochondrial dysfunction in heart failure (HF) we included mitochondrial-targeting prediction for all sORFs
by employing n-terminal protein sequence analysis using the computational programs MitoFates and MitoProt.
In addition, we have incorporated mRNA deep sequencing left ventricular samples of mice subjected to
transaortic constriction (pressure-overload HF) or permanent ligation of the left coronary artery (myocardial
infarction) at multiple stages of disease progression to identify differentially expressed sORFs in HF. To
prioritize our search, we are ranking various components for unbiased target selection and experimental
confirmation. We envision this novel database as having great importance within and beyond the
cardiovascular field for identifying novel genes with therapeutic potential.

## Key facts

- **NIH application ID:** 9977248
- **Project number:** 5F31HL143913-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Emma K Murray
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $25,391
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977248

## Citation

> US National Institutes of Health, RePORTER application 9977248, Discovery and Characterization of sORFs encoding mitochondrial peptides with a Role in Heart Failure (5F31HL143913-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9977248. Licensed CC0.

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