在PRKCZ未翻译区域的遗传多态性影响mRNA结构,稳定性和结合点
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
概括
蛋白激酶C Zeta (PRKCZ) 基因影响转录因子和miRNA结合的未翻译区域 (UTR) 的遗传变异. 这项研究确定了有害的PRKCZ变异及其对基因调节的影响,为治疗策略铺平了道路.
科学领域:
- 遗传学和分子生物学
- 生物信息学是一种生物信息学.
- 基因组法规 基因组法规
背景情况:
- 未翻译区域 (UTR) 在基因调节中起着至关重要的作用,影响表型和疾病.
- 蛋白激酶C Zeta (PRKCZ) 与各种疾病有关,但其调节机制尚未得到充分研究.
- 了解UTR变异对PRKCZ的影响对于疾病关联研究至关重要.
研究的目的:
- 研究PRKCZ基因的5'和3'未翻译区域 (UTR) 中遗传变异的功能影响.
- 分析这些变异如何影响转录因子 (TF) 和微RNA (miRNA) 结合位点.
- 探索UTR变异对RNA二级结构,表达定量特征位点 (eQTLs) 和基因变异耐受性的影响.
主要方法:
- 从Ensembl,COSMIC和gnomAD.下载了PRKCZ基因变异的数据.
- 使用RegulomeDB.DB评估UTR变异的功能影响.
- 分析了阿里巴巴的转录因子结合部位 (TFBS) 和PolymiRTS和SNPinfo.com的miRNA结合部位.
- 进行了RNA二次结构,eQTL和变异耐受性分析.
主要成果:
- 在中华人民共和国发现了25种有害的5' UTR和24种有害的3' UTR变异.
- 发现5' UTR变异改变YY1,抑制剂和Oct1的结合部位,而3' UTR变异影响AP-2alpha,AhR,Da,GR和USF结合.
- 观察到RNA二次结构,miRNA结合部位的变化,并确定了一种eQTL变异,与肺和甲状腺组织中的PRKCZ表达相关.
- 发现PRKCZ是一种不耐受基因,这表明它的功能重要性.
结论:
- 在PRKCZ UTRs中的遗传变异显著影响TF和miRNA结合,RNA结构和基因表达.
- 这些发现为未来研究PRKCZ作为潜在的治疗点提供了基础.
- 这项研究强调了非编码变异在疾病发病过程中的重要性.
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