SRSF7 and SRSF3 depend on RNA sequencing motifs and secondary structures to regulate Microprocessor.

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.