Johanna E. Plehn (Germany)
Johannes Gutenberg University of Mainz, AK Friedland
Institute of Pharmaceutical and Biomedical Sciences
Johanna Eleonore Plehn studied Pharmacy from 2012-2016 at the Eberhard Karl University of Tübingen in Germany. After receiving her license as a pharmacist, she completed an internship in the lab of Dr. James Hodge at the School of Physiology, Pharmacology and Neuroscience, University of Bristol. In 2017, she became a PhD student in the group of Prof. Dr. Kristina Friedland, Institute of Pharmaceutical and Biomedical Sciences (IPBW) at the Johannes Gutenberg University (JGU) of Mainz. In her thesis she is investigating mitochondrial dysfunction in relation to Alzheimer’s disease and focuses on RNA modifications and their corresponding writer enzymes. Her research approach is based on commonly used methods such as Western blots, RT and PCR, as well as sophisticated methods such as database analysis of human patients’ data and Illumina sequencing in collaboration with Prof. Dr. Mark Helm’s lab (IPBW, JGU Mainz).

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 Conference Calendar

INVOLVEMENT OF RNA MODIFICATIONS AND CORRESPONDING WRITER ENZYMES AT A SPECIFIC MITOCHONDRIAL MRNA SITE IN ALZHEIMER'S DISEASE

Session Name
0880 - MITOCHONDRIAL DEFECTS IN AD, PD (ID 61)
Session Type
SYMPOSIUM
Date
Thu, 17.03.2022
Session Time
05:15 PM - 07:15 PM
Room
ONSITE: 133-134
Lecture Time
06:00 PM - 06:15 PM
Presenter

Abstract

Aims

RNA modifications offer a new and emerging field of cellular regulation and are involved in several human diseases. However, each RNA modification must be considered individually, because depending on localization and modification level, its effects may be different. Therefore we aim to unravel the function and impact of specific RNA modifications in the mitochondrial epitranscriptome and observe their involvement in mitochondrial dysfunction during Alzheimer’s Disease.

Methods

To address specific sites in mitochondrial RNA, a sequencing based approach is used, coupled with a reverse transcription. RNA modifications are evoking specific patterns of truncation, mismatch and jumps in the complementary strand during reverse transcription. Therefore modification levels can be estimated after Illumina sequencing and a bioinformatics analysis. Writer enzymes can be characterized in different models via Western Blot or evaluation of human databases.

Results

We found that the RNA modification N1-Methyladenosine (m1A) is elevated on a specific mitochondrial mRNA site. Besides protein levels of the corresponding writer enzyme are increased in an AD cell and animal model and mRNA levels are increased in excitatory and inhibitory neurons of human AD patients. Our results suggest, that modified mRNA inhibits protein translation, probably provoking mitochondrial dysfunction.

Conclusions

Modifications of mitochondrial mRNA sites might interfere with translation and therefore impair the synthesis of mitochondrial proteins. Moreover, we demonstrate that there is a correlation of mRNA modification content, writer enzyme level and the associated synthesized protein.

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