2020
DOI: 10.1080/15476286.2020.1868139
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Bulges control pri-miRNA processing in a position and strand-dependent manner

Abstract: MicroRNAs (miRNAs) play critical roles in gene expression and numerous human diseases. The success of miRNA biogenesis is largely determined by the primary miRNA (pri-miRNA) processing by the DROSHA-DGCR8 complex, called Microprocessor. Here, we analysed the high-throughput pri-miRNA processing assays and secondary structures of pri-miRNAs to investigate the roles of bulges in the pri-miRNA processing. We found that bulges in multiple places control both the cleavage efficiency and accuracy of pri-miRNA proces… Show more

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Cited by 31 publications
(22 citation statements)
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“…More generally, a role for ncRNA in neurodegenerative diseases is emerging [ 58 ]. Many lncRNAs were found to be differentially expressed in brains of AD patients or mouse models and involved in biological processes including Aß metabolism, tau phosphorylation, neuroinflammation, synaptic plasticity and neuronal death [ 26 ]. Our results provide evidence for LINC-PINT specifically in modulating CAA pathology in AD.…”
Section: Discussionmentioning
confidence: 99%
“…More generally, a role for ncRNA in neurodegenerative diseases is emerging [ 58 ]. Many lncRNAs were found to be differentially expressed in brains of AD patients or mouse models and involved in biological processes including Aß metabolism, tau phosphorylation, neuroinflammation, synaptic plasticity and neuronal death [ 26 ]. Our results provide evidence for LINC-PINT specifically in modulating CAA pathology in AD.…”
Section: Discussionmentioning
confidence: 99%
“…Most miRNAs are derived from protein-coding genes in the human genome, but some miRNAs are derived from ncRNA-coding genes ( 26 ). Specifically, the genes encoding lncRNA are processed to form primary miRNA (pri-miRNA), and then pri-miRNA is further processed in the nucleus by Drosha/DGCR8 into a double-hairpin precursor miRNA (pre-miRNA) ( 27 ). Finally, the pre-miRNA is transported to the cytoplasm and cut into mature miRNA by Dicer ( 28 ).…”
Section: Ectopic Expression Of Lncrnas Mediates Chemotherapeutic Resistancementioning
confidence: 99%
“…The sequence motifs UG at the basal junction, UGUG at the apical junction, and CNNC at the 3 0 flanking sequence have been reported to facilitate Drosha processing (Auyeung et al, 2013;Fang and Bartel, 2015). Recent studies have further found that miRNA precursors tend to have bulge-depleted regions in the upper and lower part of the miRNA duplex (Roden et al, 2017) and that bulges in the lower and middle part of the miRNA duplex influence Drosha processing efficiency and/or precision (Li et al, 2020b(Li et al, , 2020a. Other studies have shown that the GHG motif, defined as an unmatched nucleotide other than guanosine that is flanked by two base-paired guanosines at position À7 to À5 relative to the Drosha cleavage site, can facilitate miRNA precursor processing efficiency and precision (Fang and Bartel, 2015).…”
Section: Introductionmentioning
confidence: 99%