microRNAs (miRNAs) are ~22 nt RNAs that play critical roles in gene regulation and are related to many human diseases. miRNAs are processed from primary miRNAs (pri-miRNAs) by the DROSHA-DGCR8 complex, called Microprocessor, which mainly determines the efficiency and accuracy of miRNA biogenesis. In this study, we investigated the roles of bulge in pri-miRNA processing by analysing secondary structures of human pri-miRNAs and conducting the pri-miRNA processing assays. We found that multiple bulges in different positions or strands of pri-miRNAs enhance or inhibit the cleavage activity of the Microprocessor via affecting the DROSHA subunit. Interestingly, the conserved and enriched bulges in positions 10–13 on the 5p-strand (midB_1013_5p) from the cleavage sites of the Microprocessor in...[ Read more ]

microRNAs (miRNAs) are ~22 nt RNAs that play critical roles in gene regulation and are related to many human diseases. miRNAs are processed from primary miRNAs (pri-miRNAs) by the DROSHA-DGCR8 complex, called Microprocessor, which mainly determines the efficiency and accuracy of miRNA biogenesis. In this study, we investigated the roles of bulge in pri-miRNA processing by analysing secondary structures of human pri-miRNAs and conducting the pri-miRNA processing assays. We found that multiple bulges in different positions or strands of pri-miRNAs enhance or inhibit the cleavage activity of the Microprocessor via affecting the DROSHA subunit. Interestingly, the conserved and enriched bulges in positions 10–13 on the 5p-strand (midB_1013_5p) from the cleavage sites of the Microprocessor inhibit the misorientation of DROSHA on pri-miRNAs, then increase miRNA expression. This study enhanced our understanding of pri-miRNA processing and proposed the roles of bulges in miRNA biogenesis by various mechanisms, including single nucleotide polymorphisms.