Abstract
microRNA biogenesis and senescence
Highlights
To examine the impact of global disruption of miRNA activity in primary cells we focused on DGCR8, an essential factor required for early steps of miRNA synthesis
Together with the ribonuclease DROSHA, DGCR8 forms the so-called Microprocessor nuclear complex, which is responsible of the processing of primary miRNA transcripts to generate the pre-miRNA intermediates that are further processed by Dicer to yield mature miRNAs [3]
We found that the disruption of miRNA biogenesis by silencing of DGCR8 behaved as a potent pro-senescence stimulus in human and mouse primary fibroblasts, leading to a clear reduction in proliferation, and the acquisition of classical senescence markers including flattened morphology, SA-BetaGal activity or formation of SAHF
Summary
This phenotype is characterized by a specific gene expression program, which is controlled by key transcriptional regulators as well as by global and genespecific epigenetic changes. Our recent results [2] provide new evidence that supports the notion that microRNAmediated control of gene expression plays a critical regulatory role in cellular senescence. MicroRNAs are small noncoding RNAs that negatively regulate gene expression primarily through the degradation or translation inhibition of mRNAs with complementary sequences.
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