To discover and thoroughly demonstrate the newly identified noncanonical cleavage mechanism, the Hong Kong University of Science and Technology (HKUST) research team, led by Prof. Tuan Anh Nguyen, Assistant Professor of the Division of Life Science, used several sophisticated techniques, such as miRNA sequencing, pri-miRNA structure analysis, and high-throughput pri-miRNA cleavage assays for approximately 260,000 pri-miRNA sequences. In contrast to the canonical mechanism, the noncanonical mechanism does not rely on several essential protein and RNA elements required for the canonical mechanism. The study also revealed previously unrecognized DROSHA recognition sites (DRES), which are critical for noncanonical cleavage but can also function in the canonical cleavage mechanism. Furthermore, the study highlights the evolutionary aspect of this noncanonical cleavage mechanism, revealing that it is conserved across several animal species. This finding suggests that the noncanonical mechanism plays a significant role in the evolution of miRNA biogenesis and regulation. Read More...

The image depicts the noncanonical processing model of Microprocessors in action. The Microprocessor complex consists of DROSHA, shown in blue, and the DGCR8 dimer, represented in green. Arrowheads indicate the double cleavage action of DROSHA on pri-miRNAs. The noncanonical processing substrate is characterized by a short stem of approximately 28 base pairs and DRES (DROSHA Recognition Sites). This noncanonical mechanism is conserved across a variety of animal species.
Scientific Breakthroughs & Discoveries