Short tandem repeat variants are possibly associated with RNA secondary structure and gene expression

Area of Science:

• Genomics
• Computational Biology
• Molecular Biology

Background:

• Short tandem repeats (STRs) are prevalent in the human genome and linked to various diseases.
• STR variants can influence DNA structure and gene expression, but their impact on RNA structure is less understood.

Purpose of the Study:

• To investigate how STR variants affect RNA secondary structure and accessibility.
• To predict RNA structural changes using computational tools and correlate them with gene expression data.

Main Methods:

• Utilized data from the 1000 Genomes Project and ViennaRNA computational tools.
• Identified transcribed STRs impacting RNA folding (fSTRs) and analyzed their association with gene expression.
• Characterized fSTRs based on repeat motif, length, and gene annotation.

Main Results:

• Identified 17,255 transcribed STRs affecting RNA folding (fSTRs), with 356 potentially linked to gene expression.
• Found that transcribed fSTR variants predominantly affect RNA multiloops and external loops.
• Demonstrated that repeat motif influences RNA accessibility, confirmed by simulation.

Conclusions:

• STR variants can significantly alter RNA secondary structure and accessibility.
• Computational prediction of RNA structural changes induced by STRs is feasible.
• Findings provide a foundation for understanding STRs' role in gene regulation and disease.