DDX21 interacts with nuclear AGO2 and regulates the alternative splicing of <i>SMN2</i>

Abstract

AGO2 is the only member of mammalian Ago protein family that possesses the catalytic activity and plays a central role in gene silencing. Recently researches reported that multiple gene silencing factors, including AGO2, function in the nuclei. The molecular mechanisms of the gene silencing factors functioning in nuclei are conducive to comprehend the roles of gene silencing in pretranslational regulation of gene expression. Here, we report that AGO2 interacts with DDX21 indirectly in an RNA-dependent manner by Co-IP and GST-Pulldown assays and the 2 proteins present nuclei foci in the immunofluorescence experiments. We found that DDX21 up-regulated the protein level of AGO2 and participated in target gene, SNM2, alternative splicing involved in AGO2 by the indirect interaction with AGO2, which produced different transcripts of SMN2 in discrepant expression level. This study laid important experiment foundation for the further analysis of the nuclear functions of gene silencing components.