Stimuli-dependent cleavage of Dicer during apoptosis.

miRNAs (microRNAs) play important roles in diverse physiological processes, including stress response, apoptosis and carcinogenesis. Even though the role of individual miRNAs has been demonstrated, expression of proteins involved in miRNA production in response to acute stress or harmful agents has not been extensively investigated. Here, we have studied the role of Dicer, one of the central proteins of the miRNA processing machinery during apoptosis, and show that down-regulation of Dicer results in accelerated apoptosis of HeLa cells, triggered by TNFalpha (tumour necrosis factor alpha). We have also investigated the integrity of Dicer, and provide evidence that Dicer is a target for caspases during apoptosis. The cleavage of Dicer is stimulidependent and more pronounced when apoptosis is induced by PKC (protein kinase C) inhibitors, and can also be observed in HIV-1-infected cells at late stages of infection. Thus the apoptotic machinery may regulate the miRNA pathway by affecting individual proteins, such as Dicer.