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Published on: February 23, 2021
SRSF7 and SRSF3 depend on RNA sequencing motifs and secondary structures to regulate Microprocessor
Minh Ngoc Le1, Trung Duc Nguyen1, Tuan Anh Nguyen2
1Division of Life Science, The Hong Kong University of Science & Technology, Hong Kong, China.
Abstract:
Human Microprocessor cleaves pri-miRNAs to initiate miRNA biogenesis. The accuracy and efficiency of Microprocessor cleavage ensure appropriate miRNA sequence and expression and thus its proper gene regulation. However, Microprocessor cleaves many pri-miRNAs incorrectly, so it requires assistance from many cofactors. For example, SRSF3 enhances Microprocessor cleavage by interacting with the CNNC motif in pri-miRNAs. However, whether SRSF3 can function with other motifs and/or requires the motifs in a certain secondary structure is unknown. In addition, the function of SRSF7 (a paralog of SRSF3) in miRNA biogenesis still needs to be discovered. Here, we demonstrated that SRSF7 could stimulate Microprocessor cleavage. In addition, by conducting high-throughput pri-miRNA cleavage assays for Microprocessor and SRSF7 or SRSF3, we demonstrated that SRSF7 and SRSF3 function with the CRC and CNNC motifs, adopting certain secondary structures. In addition, SRSF7 and SRSF3 affect the Microprocessor cleavage sites in human cells. Our findings demonstrate the roles of SRSF7 in miRNA biogenesis and provide a comprehensive view of the molecular mechanism of SRSF7 and SRSF3 in enhancing Microprocessor cleavage.
Insights
SRSF7 and SRSF3 enhance Microprocessor cleavage of pri-miRNAs by recognizing specific motifs and secondary structures, ensuring accurate miRNA biogenesis and gene regulation.
Area of Science:
- Molecular Biology
- RNA Biology
- Gene Regulation
Background:
- Microprocessor complex initiates microRNA (miRNA) biogenesis by cleaving precursor miRNAs (pri-miRNAs).
- Cofactors like SRSF3 assist Microprocessor in cleaving pri-miRNAs, but the full mechanisms and roles of other factors remain unclear.
- The function of SRSF7, a paralog of SRSF3, in miRNA biogenesis is largely undiscovered.
Purpose of the Study:
- To investigate the role of SRSF7 in miRNA biogenesis.
- To elucidate the molecular mechanisms by which SRSF7 and SRSF3 enhance Microprocessor cleavage.
- To identify sequence motifs and structural requirements for cofactor-assisted Microprocessor activity.
Main Methods:
- High-throughput pri-miRNA cleavage assays were performed.
- Assays involved Microprocessor complex, SRSF7, and SRSF3.
- Analysis of cofactor interactions with pri-miRNA motifs and secondary structures in human cells.
Main Results:
- SRSF7 was demonstrated to stimulate Microprocessor cleavage.
- Both SRSF7 and SRSF3 were shown to function with CRC and CNNC motifs.
- These motifs require specific secondary structures for cofactor-mediated cleavage.
- SRSF7 and SRSF3 influence Microprocessor cleavage sites within human cells.
Conclusions:
- SRSF7 plays a significant role in miRNA biogenesis.
- SRSF7 and SRSF3 enhance Microprocessor activity through specific motif recognition and structural requirements.
- These findings provide a comprehensive understanding of the molecular mechanisms governing Microprocessor-cofactor interactions in miRNA processing.
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