G-Quadruplex and i-Motif Structures in the SHMT1 5'UTR Modulate Gene Expression

Area of Science:

• Genetics
• Molecular Biology
• Neuroscience

Background:

• Multiple sclerosis (MS) is a fatal neurodegenerative disease with no effective cure.
• Gene dysregulation, particularly in DNA methylation, is implicated in MS progression.
• Targeting DNA and RNA secondary structures offers a potential therapeutic strategy for MS.

Purpose of the Study:

• To investigate the role of DNA and RNA secondary structures in the regulation of Serine hydroxy methyltransferase 1 (SHMT1) in MS.
• To characterize G-quadruplex (GQ) and i-motif (iM) structures in the SHMT1 gene.
• To explore the potential of these structures as therapeutic targets for MS.

Main Methods:

• Identification and characterization of GQ and iM structures in the SHMT1 5' untranslated region (DNA) and mRNA.
• Reporter gene assays to assess the impact of GQ/iM structures on gene expression.
• Analysis of SHMT1 gene expression in MS patients.

Main Results:

• A hybrid 3+1 GQ/iM structure was identified in the SHMT1 DNA 5' UTR.
• A parallel GQ structure was found in the SHMT1 mRNA.
• These GQ/iM structures were shown to suppress reporter gene mRNA levels and protein expression.

Conclusions:

• GQ/iM structures in SHMT1 play a crucial role in regulating its expression.
• These structures represent a potential therapeutic target for MS intervention.
• Further research into targeting these structures could lead to novel MS treatments.