MicroRNA biogenesis pathway alterations in aging

J. Sanz-Ros, C. Mas-Bargues, Nekane Romero-García, Javier Huete-Acevedo, M. Dromant, C. Borrás
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引用次数: 1

Abstract

Aging is characterized by genomic instability and dysregulation of gene expression. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in post-transcriptional gene regulation. This work explores the impact of dysregulated miRNA biogenesis on the aging process. During aging, alterations in the transcription of primary miRNAs (pri-miRNAs) occur due to genomic changes, DNA damage, and epigenetic modifications. The microprocessor complex, comprising DGCR8 and Drosha proteins, is vital for pri-miRNA processing. Age-related changes in this complex affect miRNA biogenesis and miRNA expression profiles, linking these alterations with age-related conditions. Conversely, interventions like caloric restriction and mTOR inhibition enhance microprocessor activity, suggesting a connection between microprocessor function, aging-related pathways, and lifespan extension. Exportin-5 mediates the transport of pre-miRNAs from the nucleus to the cytoplasm. Although the role of miRNA export in aging is not well understood, accelerated export of pre-miRNAs is observed in response to DNA damage, and nucleocytoplasmic transport has been linked to cellular senescence. Dicer is responsible for processing pre-miRNAs into mature miRNAs. Reduced Dicer expression during aging is reported in various organisms and tissues and is associated with premature aging phenotypes. Conversely, the upregulation of Dicer improves stress resistance and metabolic adaptations induced by caloric restriction and exercise training. Understanding the role of miRNA biogenesis disruption in aging provides insights into the molecular mechanisms of aging and age-related diseases. Targeting this pathway may hold promise for therapeutic strategies and contribute to healthy aging.
衰老过程中MicroRNA生物发生途径的改变
衰老的特征是基因组不稳定和基因表达失调。MicroRNAs (miRNAs)是一种小的非编码rna,在转录后基因调控中起着至关重要的作用。这项工作探讨了miRNA生物发生失调对衰老过程的影响。在衰老过程中,由于基因组变化、DNA损伤和表观遗传修饰,初级miRNAs (pri-miRNAs)的转录发生改变。由DGCR8和Drosha蛋白组成的微处理器复合物对pri-miRNA加工至关重要。该复合物的年龄相关变化影响miRNA的生物发生和miRNA表达谱,将这些变化与年龄相关的疾病联系起来。相反,热量限制和mTOR抑制等干预措施可以增强微处理器的活性,这表明微处理器功能、衰老相关途径和寿命延长之间存在联系。export -5介导前mirna从细胞核到细胞质的运输。尽管miRNA输出在衰老中的作用尚不清楚,但在DNA损伤的反应中可以观察到pre-miRNA的加速输出,并且核细胞质运输与细胞衰老有关。Dicer负责将pre- mirna加工成成熟的mirna。据报道,在各种生物体和组织中,衰老过程中Dicer表达的减少与早衰表型有关。相反,Dicer的上调可以改善由热量限制和运动训练引起的应激抵抗和代谢适应。了解miRNA生物发生中断在衰老中的作用,有助于深入了解衰老和年龄相关疾病的分子机制。靶向这一途径可能为治疗策略带来希望,并有助于健康衰老。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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