The Transcription of hERG1NP in Human Cardiac Development – UROP Spring Symposium 2024

The Transcription of hERG1NP in Human Cardiac Development

Pamela Ruzycki

Pronouns: she/her

Research Mentor(s): David Jones
Research Mentor School/College/Department: Pharmacology / Medicine
Program:
Authors: David Jones, Abhilasha Jain, Pamela Ruzycki
Session: Session 2: 10:00 am – 10:50 am
Poster: 22

Abstract

The human ether-a-go-go related gene (hERG, aka KCNH2 ) encodes the voltage-gated potassium channel made up of two nearly identical subunits, hERG1a and hERG1b, that are crucial for the repolarization of cardiac action potential. A dysfunctional channel is correlated to sudden infant death syndrome (SIDS) and cardiac arrythmia, as well as cardiac death. Recent work from our lab has identified a novel subdomain of hERG1 that is targeted to the nucleus in immature cardiac cells, including human stem cell-derived cardiomyocytes (hiPSC-CMs). We have named this polypeptide hERG1NP. hERG1NP appears to be homologous to the C-terminus of hERG1. The mechanism of hERG1NP biogenesis is not known. A nuclear localization sequence is present in hERG1NP that maps to exon 11. We hypothesize that an internal transcriptional start site is present upstream of the of this position.To test this hypothesis, I will use RACE PCR to identify a potential hERG1NP-mRNA encoding sequence. Isolating mRNA from induced pluripotent stem cells (iPSCs) and wild type cells (WT), I will use reverse transcriptase to first produce cDNA and then amplify the target sequence range using a variety of gene-specific primers (GSPs) and primers targeting the poly-T tail of the cDNA. This work will aid in determining the mechanism of hERG1NP’s transcription as well as generate further hypotheses on its function in cardiac action potential.

Biomedical Sciences, Interdisciplinary, Natural/Life Sciences

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