Investigation of UTR Variants by Computational Approaches Reveal Their Functional Significance in PRKCI Gene...

Area of Science:

• Genetics and Molecular Biology
• Cancer Research
• Gene Regulation

Background:

• Single nucleotide polymorphisms (SNPs) are genetic variations linked to various diseases, including cancers.
• Non-coding regions, particularly Untranslated Regions (UTRs), play crucial roles in gene expression and disease pathophysiology.
• The PRKCI gene's UTRs are implicated in disease, making their genetic variations important for study.

Purpose of the Study:

• To investigate the functional impact of UTR-localized SNPs in the PRKCI gene on miRNA interactions, mRNA stability, and transcription factor binding.
• To identify specific PRKCI UTR SNPs associated with disease-related expression patterns and potential functional consequences.

Main Methods:

• Utilized bioinformatics tools (PolymiRTS, miRNASNP, MicroSNIper, GTEx, RNAfold, PROMO, GeneCards, RegulomeDB) to analyze UTR SNPs.
• Evaluated SNP associations with microRNAs (miRNAs), gene expression, mRNA structure, transcription factor binding sites, and genetic intolerance.
• Assessed linkage disequilibrium and disease associations for identified SNPs.

Main Results:

• Identified 31 UTR SNPs in PRKCI, with 23 showing associations with miRNAs.
• Two SNPs (rs140672226, rs2650220) linked to expression in stomach and esophagus mucosa.
• Several 3' and 5' UTR SNPs predicted to destabilize mRNA structure and affect transcription factor binding; PRKCI is intolerant to loss-of-function variants.

Conclusions:

• UTR SNPs in the PRKCI gene significantly impact miRNA binding, mRNA stability, and transcription.
• These findings suggest a substantial functional role for PRKCI UTR SNPs in disease development.
• Further experimental validation is recommended for diagnostic and therapeutic applications.