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

Hania Shah; Khushbukhat Khan; Yasmin Badshah; Naeem Mahmood Ashraf; Maria Shabbir; Janeen H Trembley; Tayyaba Afsar; Ali Abusharha; Suhail Razak

doi:10.3390/genes14020247

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

Genes (Basel). 2023 Jan 18;14(2):247. doi: 10.3390/genes14020247.

Authors

Affiliations

¹ Department of Healthcare Biotechnology, Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad 45860, Pakistan.
² School of Biochemistry and Biotechnology, University of the Punjab, Lahore 54590, Pakistan.
³ Minneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USA.
⁴ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
⁵ Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
⁶ Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.
⁷ Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia.

Abstract

Single nucleotide polymorphisms (SNPs) are associated with many diseases including neurological disorders, heart diseases, diabetes, and different types of cancers. In the context of cancer, the variations within non-coding regions, including UTRs, have gained utmost importance. In gene expression, translational regulation is as important as transcriptional regulation for the normal functioning of cells; modification in normal functions can be associated with the pathophysiology of many diseases. UTR-localized SNPs in the PRKCI gene were evaluated using the PolymiRTS, miRNASNP, and MicroSNIper for association with miRNAs. Furthermore, the SNPs were subjected to analysis using GTEx, RNAfold, and PROMO. The genetic intolerance to functional variation was checked through GeneCards. Out of 713 SNPs, a total of thirty-one UTR SNPs (three in 3' UTR region and twenty-nine in 5' UTR region) were marked as ≤2b by RegulomeDB. The associations of 23 SNPs with miRNAs were found. Two SNPs, rs140672226 and rs2650220, were significantly linked with expression in the stomach and esophagus mucosa. The 3' UTR SNPs rs1447651774 and rs115170199 and the 5' UTR region variants rs778557075, rs968409340, and 750297755 were predicted to destabilize the mRNA structure with substantial change in free energy (∆G). Seventeen variants were predicted to have linkage disequilibrium with various diseases. The SNP rs542458816 in 5' UTR was predicted to put maximum influence on transcription factor binding sites. Gene damage index(GDI) and loss of function (o:e) ratio values for PRKCI suggested that the gene is not tolerant to loss of function variants. Our results highlight the effects of 3' and 5' UTR SNP on miRNA, transcription and translation of PRKCI. These analyses suggest that these SNPs can have substantial functional importance in the PRKCI gene. Future experimental validation could provide further basis for the diagnosis and therapeutics of various diseases.

Keywords: 3′ UTR; 5′ UTR; PRKCI; SNP; miRNA; non-coding region.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions
5' Untranslated Regions
Gene Expression Regulation
Humans
MicroRNAs* / genetics
Neoplasms* / genetics
Polymorphism, Single Nucleotide
Protein Kinase C* / genetics

Substances

3' Untranslated Regions
5' Untranslated Regions
MicroRNAs
protein kinase C lambda
Protein Kinase C

Grants and funding

We are grateful to the deanship of the researcher support project number (RSPD2023R653), King Saud University, Riyadh Saudi Arabia for funding this project.