Zaichenko D M, Mikryukova A A, Astafeva I R, Malakho S G, Kubatiev A A, Moskovtsev A A
Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.
Botkin City Clinical Hospital, Moscow Health Department, Moscow, 125284 Russia.
Mol Biol (Mosk). 2023 Jul-Aug;57(4):671-686.
MicroRNAs are small noncoding RNAs that regulate gene expression; stabilize the cell phenotype; and play an important role in cell differentiation, development, and apoptosis. A canonical microRNA biogenesis pathway includes several posttranscriptional steps of processing and transport and ends with cytoplasmic cleavage of pre-miRNA by type III ribonuclease DICER to form a mature duplex, which is included in RISC. MicroRNA biogenesis and role in cell stress are still poorly understood. Using flow cytometry and high-throughput analysis of gene expression, we have shown that chronic endoplasmic reticulum (ER) stress, which is associated with improper protein folding in the ER, induce a cellular senescence phenotype in fibroblast-like FRSN cells. While acute ER stress can reduce miRNA biogenesis, chronic stress does not cause a significant drop in global microRNA expression and is accompanied by only a slight decrease in DICER1 mRNA expression. Heterogeneity with respect to lysosomal β-galactosidase activity was found to increase in the cell population exposed to ER stress. We do not exclude induced cell heterogeneity regarding expression of components of the microRNA biogenesis pathway.
微小RNA是一类小的非编码RNA，可调控基因表达、稳定细胞表型，并在细胞分化、发育及凋亡过程中发挥重要作用。典型的微小RNA生物合成途径包括几个转录后加工和运输步骤，最终由III型核糖核酸酶DICER对前体微小RNA进行细胞质切割，形成成熟双链体，该双链体被纳入RNA诱导沉默复合体（RISC）。微小RNA的生物合成及其在细胞应激中的作用仍知之甚少。通过流式细胞术和基因表达高通量分析，我们发现与内质网中蛋白质错误折叠相关的慢性内质网应激可在成纤维样FRSN细胞中诱导细胞衰老表型。虽然急性内质网应激可减少微小RNA的生物合成，但慢性应激不会导致整体微小RNA表达显著下降，仅伴随着DICER1 mRNA表达略有降低。在暴露于内质网应激的细胞群体中，发现溶酶体β-半乳糖苷酶活性的异质性增加。我们不排除在微小RNA生物合成途径成分表达方面诱导的细胞异质性。
