Abstract:
:The 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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Nguyen TL,Nguyen TD,Bao S,Li S,Nguyen TAdoi
10.1093/nar/gkaa018subject
Has Abstractpub_date
2020-03-18 00:00:00pages
2579-2593issue
5eissn
0305-1048issn
1362-4962pii
5709711journal_volume
48pub_type
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