| Autor: |
Zaichenko DM; Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia., Mikryukova AA; Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia., Astafeva IR; Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia., Malakho SG; Botkin City Clinical Hospital, Moscow Health Department, Moscow, 125284 Russia., Kubatiev AA; Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.; Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation, Moscow, 125993 Russia., Moskovtsev AA; Institute of General Pathology and Pathophysiology, Moscow, 125315 Russia.; Medical Academy of Continuing Professional Education, Ministry of Health of the Russian Federation, Moscow, 125993 Russia.; bioinf@mail.ru. |
| Abstrakt: |
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. |
