AI Article Synopsis
- The Microprocessor, made up of DROSHA and DGCR8, plays a key role in the processing of primary microRNAs (pri-miRNAs), with DGCR8 enhancing the efficiency and accuracy of this process by interacting with a specific UGU motif.
- Important findings from the study show that the RNA-binding domain of DGCR8 (Rhed) interacts with the UGU motif and that three specific amino acids (461-463) are crucial for this interaction, impacting the Microprocessor's ability to process UGU-pri-miRNAs in human cells.
- The research highlights how this interaction aids in distinguishing between different types of pri-miRNAs, which ultimately affects miRNA expression levels in human cells.
Article Abstract
Microprocessor, composed of DROSHA and DGCR8, processes primary microRNAs (pri-miRNAs) in miRNA biogenesis. Its cleavage efficiency and accuracy are enhanced because DGCR8 interacts with the apical UGU motif of pri-miRNAs. However, the mechanism and influence of DGCR8-UGU interaction on cellular miRNA expression are still elusive. In this study, we demonstrated that Rhed (i.e., the RNA-binding heme domain, amino acids 285-478) of DGCR8 interacts with UGU. In addition, we identified three amino acids 461-463 in Rhed, which are critical for the UGU interaction and essential for Microprocessor to accurately and efficiently process UGU-pri-miRNAs in vitro and UGU-miRNA expression in human cells. Furthermore, we found that within the DGCR8 dimer, the amino acids 461-463 from one monomer are capable of discriminating between UGU- and noUGU-pri-miRNAs. Our findings improve the current understanding of the substrate-recognizing mechanism of DGCR8 and implicate the roles of this recognition in differentiating miRNA expression in human cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334207 | PMC |
| http://dx.doi.org/10.1038/s42003-020-1071-5 | DOI Listing |
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