Peptides Targeting RNA m 6 A Methylations Influence the Viability of Cancer Cells

N6-methyladenosine (m A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m A levels in transcriptome are tightly correlated to expression levels of m A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are obse...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:ChemMedChem 2023-02, Vol.18 (4), p.e202200549
Hauptverfasser: Rauff, Rushdhi, Abedeera, Sudeshi M, Schmocker, Stefani, Xie, Jiale, Abeysirigunawardena, Sanjaya C
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:N6-methyladenosine (m A) is the most abundant nucleotide modification observed in eukaryotic mRNA. Changes in m A levels in transcriptome are tightly correlated to expression levels of m A methyltransferases and demethylases. Abnormal expression levels of methyltransferases and demethylases are observed in various diseases and health conditions such as cancer, male infertility, and obesity. This research explores the efficacy of m A-modified RNA as an anticancer drug target. We discovered a 12-mer peptide that binds specifically to m A-modified RNA using phage display experiments. Our fluorescence-based assays illustrate the selected peptide binds to methylated RNA with lower micromolar affinity and inhibit the binding of protein FTO, a demethylase enzyme specific to m A modification. When cancer cell lines were treated with mtp1, it led to an increase in m A levels and a decrease in cell viability. Hence our results illustrate the potential of mtp1 to be developed as a drug for cancer.
ISSN:1860-7179
1860-7187
DOI:10.1002/cmdc.202200549