Noncanonical cleavage mechanism sheds light on miRNA production

Scientists at the Hong Kong University of Science and Technology (HKUST) have made a groundbreaking discovery in the field of molecular biology. Led by Prof. Tuan Anh Nguyen, the research team has identified a previously unknown noncanonical cleavage mechanism involved in the production of microRNAs (miRNAs).

MiRNAs are small RNA molecules that play a crucial role in regulating gene activity and controlling various biological processes, including cell growth, development, and immunity. The production of miRNAs involves a complex called the Microprocessor (MP) complex, which processes primary miRNA transcripts (pri-miRNAs) into mature miRNAs.

Until now, the molecular mechanisms of miRNA production have been primarily explained by the canonical pri-miRNA processing mechanism. However, this mechanism fails to account for the processing of a significant number of pri-miRNAs due to their structural and sequence diversity.

In their study, the HKUST research team used advanced techniques such as miRNA sequencing, pri-miRNA structure analysis, and high-throughput pri-miRNA cleavage assays to investigate approximately 260,000 pri-miRNA sequences. Their research unveiled a noncanonical cleavage mechanism that complements the canonical mechanism and provides an explanation for the processing of previously unexplained pri-miRNAs.

Key findings from the study include the discovery and comprehensive characterization of the noncanonical miRNA production mechanism in animals. This mechanism relies on previously unrecognized DROSHA recognition sites (DRES) that play a critical role in the cleavage process. The study also demonstrated the conservation of this mechanism across different animal species, highlighting its evolutionary significance in miRNA biogenesis.

The discovery of the noncanonical mechanism has significant implications for molecular biology research. It allows for the exploration of a wider range of substrates for the MP complex, potentially leading to the identification of novel pri-miRNAs and other RNA substrates processed through this mechanism. Additionally, the noncanonical mechanism suggests broader cellular functions for the MP complex, paving the way for the discovery of new roles in gene regulation and cellular processes.

Furthermore, the conservation of the noncanonical mechanism across animal species, particularly in worms like C. elegans and C. briggsae, indicates its importance in the evolution of miRNA biogenesis pathways. Future studies can delve deeper into the evolutionary aspects of both canonical and noncanonical mechanisms, shedding light on the development and diversification of miRNA biogenesis pathways in animals.

In conclusion, the discovery of the noncanonical cleavage mechanism in miRNA biogenesis represents a significant breakthrough in the field of molecular biology. It opens up new avenues for research, expands our understanding of miRNA production, and has implications for gene regulation, cellular processes, and the evolutionary history of miRNA biogenesis in animals.

Source: Hong Kong University of Science and Technology

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