Related Experiment Video

Updated: Jun 13, 2025

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
10:05

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle

Published on: March 5, 2019

6.4K

Genetic polymorphism in untranslated regions of PRKCZ influences mRNA structure, stability and binding sites

Aneela Mustafa1, Maria Shabbir2, Yasmin Badshah1

  • 1Department of Healthcare BiotechnologyAtta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Sector H-12, Islamabad, 44000, Pakistan.

BMC Cancer
|September 13, 2024
PubMed
Abstract

Insights

Genetic variants in untranslated regions (UTRs) of the Protein kinase C Zeta (PRKCZ) gene impact transcription factor and miRNA binding. This research identifies detrimental PRKCZ variants and their effects on gene regulation, paving the way for therapeutic strategies.

Area of Science:

  • Genetics and Molecular Biology
  • Bioinformatics
  • Genomic Regulation

Background:

  • Untranslated regions (UTRs) play a crucial role in gene regulation, influencing phenotype and disease.
  • Protein kinase C Zeta (PRKCZ) is implicated in various disorders, but its regulatory mechanisms are underexplored.
  • Understanding UTR variants' impact on PRKCZ is vital for disease association studies.

Purpose of the Study:

  • To investigate the functional impact of genetic variants in the 5' and 3' untranslated regions (UTRs) of the PRKCZ gene.
  • To analyze how these variants affect transcription factor (TF) and microRNA (miRNA) binding sites.
  • To explore the influence of UTR variants on RNA secondary structure, expression quantitative trait loci (eQTLs), and gene variation tolerance.

Main Methods:

  • Downloaded PRKCZ gene variant data from Ensembl, COSMIC, and gnomAD.
  • Assessed functional impact of UTR variants using RegulomeDB.
  • Analyzed transcription factor binding sites (TFBS) with Alibaba and miRNA binding sites with PolymiRTS and SNPinfo.
  • Performed RNA secondary structure, eQTLs, and variation tolerance analyses.

Main Results:

  • Identified 25 detrimental 5' UTR and 24 detrimental 3' UTR variants in PRKCZ.
  • Discovered that 5' UTR variants alter binding sites for YY1, repressor, and Oct1, while 3' UTR variants affect AP-2alpha, AhR, Da, GR, and USF binding.
  • Observed alterations in RNA secondary structure, miRNA binding sites, and identified one eQTL variant associated with PRKCZ expression in lung and thyroid tissues.
  • PRKCZ was found to be an intolerant gene, suggesting functional importance.

Conclusions:

  • Genetic variants within PRKCZ UTRs significantly impact TF and miRNA binding, RNA structure, and gene expression.
  • These findings provide a foundation for future research into PRKCZ as a potential therapeutic target.
  • The study highlights the importance of non-coding variants in disease pathogenesis.
Keywords:
In-silico toolsNon-coding SNPsOncological disordersPRKCZUTRmiRNA

More Related Videos

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes09:44

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes

Published on: March 3, 2015

9.5K
Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling10:00

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling

Published on: October 28, 2014

28.2K

Related Concept Videos

Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
7.0K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.4K
mRNA Stability and Gene Expression02:51

mRNA Stability and Gene Expression

The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
5.6K
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
What is Gene Expression?01:36

What is Gene Expression?

A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised  of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then...
8.5K
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K