Mismatched and wobble base pairs govern primary microRNA processing by human Microprocessor

Shaohua Li, Trung Duc Nguyen, Thuy Linh Nguyen and Tuan Anh Nguyen ()
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Shaohua Li: The Hong Kong University of Science and Technology
Trung Duc Nguyen: The Hong Kong University of Science and Technology
Thuy Linh Nguyen: The Hong Kong University of Science and Technology
Tuan Anh Nguyen: The Hong Kong University of Science and Technology

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract MicroRNAs (miRNAs) are small RNAs that regulate gene expression. miRNAs are produced from primary miRNAs (pri-miRNAs), which are cleaved by Microprocessor. Microprocessor, therefore, plays a crucial role in determining the efficiency and precision of miRNA production, and thus the function of the final miRNA product. Here, we conducted high-throughput enzymatic assays to investigate the catalytic mechanism of Microprocessor cleaving randomized pri-miRNAs. We identified multiple mismatches and wobble base pairs in the upper stem of pri-miRNAs, which influence the efficiency and accuracy of their processing. The existence of these RNA elements helps to explain the alternative cleavage of Microprocessor for some human pri-miRNAs. We also demonstrated that miRNA biogenesis can be altered via modification of the RNA elements by RNA-editing events or single nucleotide polymorphisms (SNPs). These findings improve our understanding of pri-miRNA processing mechanisms and provide a foundation for interpreting differential miRNA expression due to RNA modifications and SNPs.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15674-2

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DOI: 10.1038/s41467-020-15674-2

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