Division of Anaesthesia, Sardar Women's Hospital, Ahmedabad, Gujarat, India.
Division of Anasthesia, Dreamzz IVF Centre and Women's Care, Sardar Hospital, Ahmedabad, Gujarat, India.
Curr Mol Pharmacol. 2022;15(3):517-531. doi: 10.2174/1874467214666210629164535.
The discovery of the mysterious dark matter of the genome expands our understanding of modern biology. Beyond the genome, the epigenome reveals a hitherto unknown path of key biological and functional gene control activities. Extraordinary character-P element wimpy testis-induced (PiWi)-interacting RNA (piRNA) is a type of small non-coding RNA that acts as a defender by silencing nucleic and structural invaders. PiWi proteins and piRNAs can be found in both reproductive and somatic cells, though germ line richness has been partially unravelled. The primary function is to suppress invading DNA sequences known as Transpose of Elements (TEs) that move within genomic DNA and downstream target genes via Transcriptional Gene Silencing (TGS) and Post-Translational Gene Silencing (PTGS). Germline piRNAs preserve genomic integrity, stability, sternness, and influence imprinting expression. The novel roles of somatic tissue-specific piRNAs have surprised researchers. In metazoans, including humans, piRNA regulates neurodevelopmental processes. The PiWi pathway regulates neural heterogeneity, neurogenesis, neural plasticity, and transgenerational inheritance of adaptive and long-term memory. Dysregulated piRNA causes neurodevelopmental, neurodegenerative, and psychiatric illness. A faulty piRNA signature results in inadvertent gene activation via TE activation, incorrect epigenetic tags on DNA, and/or histones. Imprinting expression is influenced by germline piRNAs, which maintain genomic integrity, stability, and sternness. New roles for piRNAs specific to somatic tissues have been discovered. Metazoans, including humans, are regulated by piRNA. In addition, the PiWi pathway regulates neuronal heterogeneity and neurogenesis as well as brain plasticity and transgenerational inheritance of adaptive and long-term memory. When piRNA is dysregulated, it can lead to neurodegenerative and psychiatric illnesses. Inappropriate gene activation or inactivation is caused by aberrant piRNA signatures, TE activation, inappropriate epigenetic marks on DNA, and/or histones. Defective piRNA regulation causes abnormal brain development and neurodegenerative aetiology, which promotes life-threatening disorders. Exemplification of exciting roles of piRNA is still in its early stages, so future research may expand on these observations using novel techniques and launch them as potential biomarkers for diagnostics and therapeutics. In this review, we summarised the potential gene molecular role of piRNAs in regulating neurobiology and serving as novel biomarkers and therapeutic targets for life-threatening disease.
基因组神秘暗物质的发现拓展了我们对现代生物学的理解。除了基因组，表观基因组揭示了一条以前未知的关键生物和功能基因调控活动的途径。特别的是，P 元素瘦弱睾丸诱导（Piwi）相互作用 RNA（piRNA）是一种小的非编码 RNA，通过沉默核酸和结构入侵物发挥防御作用。Piwi 蛋白和 piRNA 可在生殖细胞和体细胞中找到，尽管生殖系的丰富度已经部分揭示。其主要功能是抑制称为转座元件（TEs）的入侵 DNA 序列，这些序列通过转录基因沉默（TGS）和翻译后基因沉默（PTGS）在基因组 DNA 内和下游靶基因中移动。生殖系 piRNA 可保持基因组的完整性、稳定性、严厉性，并影响印迹表达。体细胞组织特异性 piRNA 的新作用令研究人员感到惊讶。在后生动物中，包括人类，piRNA 调节神经发育过程。PiWi 途径调节神经异质性、神经发生、神经可塑性以及适应性和长期记忆的跨代遗传。piRNA 失调会导致神经发育障碍、神经退行性疾病和精神疾病。错误的 piRNA 特征会导致通过 TE 激活、DNA 上错误的表观遗传标记和/或组蛋白而导致意外的基因激活。生殖系 piRNA 影响印迹表达，保持基因组的完整性、稳定性和严厉性。已经发现了特定于体细胞组织的 piRNA 的新作用。后生动物，包括人类，受 piRNA 调控。此外，PiWi 途径还调节神经元异质性和神经发生以及大脑可塑性和适应性以及长期记忆的跨代遗传。当 piRNA 失调时，会导致神经退行性疾病和精神疾病。异常的基因激活或失活是由异常的 piRNA 特征、TE 激活、DNA 上不适当的表观遗传标记和/或组蛋白引起的。piRNA 调节异常会导致异常的大脑发育和神经退行性病因，从而导致危及生命的疾病。piRNA 作用的令人兴奋的例证仍处于早期阶段，因此未来的研究可能会使用新的技术扩展这些观察结果，并将其作为潜在的生物标志物用于诊断和治疗。在这篇综述中，我们总结了 piRNA 调节神经生物学的潜在基因分子作用，并作为潜在的生物标志物和治疗靶点，用于治疗危及生命的疾病。
