MOLECULAR MECHANISM OF MIRNA BIOGENESIS AND DOUBLE-STRANDED RNA PROCESSING IN RNA INTERFERENCE PATHWAY

Abstract

In mammalian cells, the characterization of components in the precisely-controlled miRNA biogenesis has not been well-established. Here, we report the identification of autoantigen La protein which directly binds with primary miRNA. My research indicates that La protein participates in regulating DGCR8-Drosha mediated primary miRNA processing. The molecular mechanism study may provide deep insight into analyzing the novel role of La protein in primary miRNA processing in human cells. To investigate the mechanism of RNAi in a budding yeast species Pichia stipitis, we solved the three-dimensional structure of the PsDCR1 fragment, NTD, which harbors a butterfly-like shape. The in vitro transcribed dsRNA binding and cleavage assays revealed that PsDCR1 could directly bind with dsRNA and cleave it into 22-23 nt small RNA products. In summary, the functional and structural study concerning PsDCR1 provides fresh perception into the dsRNA cleavage mechanism of the evolutionarily conserved DCR1.