The internal loops in the lower stem of primary microRNA transcripts facilitate single cleavage of human Microprocessor

Author:

Nguyen Thuy Linh1,Nguyen Trung Duc1,Bao Sheng1,Li Shaohua1,Nguyen Tuan Anh1ORCID

Affiliation:

1. Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong, China

Abstract

AbstractThe human Microprocessor complex cleaves primary microRNA (miRNA) transcripts (pri-miRNAs) to initiate miRNA synthesis. Microprocessor consists of DROSHA (an RNase III enzyme), and DGCR8. DROSHA contains two RNase III domains, RIIIDa and RIIIDb, which simultaneously cleave the 3p- and 5p-strands of pri-miRNAs, respectively. In this study, we show that the internal loop located in the lower stem of numerous pri-miRNAs selectively inhibits the cleavage of Microprocessor on their 3p-strand, thereby, facilitating the single cleavage on their 5p-strand. This single cleavage does not lead to the production of miRNA but instead, it downregulates miRNA expression. We also demonstrate that by manipulating the size of the internal loop in the lower stem of pri-miRNAs, we can alter the ratio of single-cut to double-cut products resulted from the catalysis of Microprocessor, thus changing miRNA production in the in vitro pri-miRNA processing assays and in human cells. Therefore, the oscillating level of the single cleavage suggests another way of regulation of miRNA expression and offers an alternative approach to miRNA knockdown.

Funder

Hong Kong University of Science and Technology

Croucher Foundation

Publisher

Oxford University Press (OUP)

Subject

Genetics

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