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A research team led by scientists from the Hong Kong University of Science and Technology has revealed how secondary structural RNA elements control the cleavage activity of DICER enzymes in pre-miRNAs and short hairpin RNAs
In humans, microRNAs (miRNAs) control a variety of biological processes and play important roles in various cellular functions
The accuracy of miRNA sequence and expression is largely determined by miRNA biogenesis, a process that involves DICER cleavage of miRNA precursors (pre-miRNAs) to generate miRNAs
In a paper published in Nature Communications, researchers led by Hong Kong University of Science and Technology Tuan Anh NGUYEN discovered the role of a secondary RNA element called 22-bulge in the cleavage activity of DICER for shRNA and human pre-miRNAs.
By designing an innovative artificial substrate model called bicircular shRNA, the team performed high-throughput cleavage analysis of more than 20,000 shRNAs containing different sequences and reconstructed uncleaved shRNA sequences from the cleavage products
Professor Nguyen said: "It is exciting that among the many secondary RNA elements identified in our study, we have identified a single nucleotide element, called 22-bulges, which is found on shRNAs and pre-miRNAs showed the highest cleavage precision and efficiency
"Our work allows us to understand the molecular mechanism of DICER cleavage and to decipher the function of secondary structural RNA elements in pre-miRNA/shRNA in controlling miRNA biogenesis and the KD activity of shRNA," said one of the co-authors, Trung Duc NGUYEN "From an application perspective, our findings provide an alternative approach to improving shRNA design for current gene silencing technologies, with higher KD efficiency and fewer off-target effects," explained the researchers
article title
Secondary structure RNA elements control the cleavage activity of DICER