A new study published in Molecular Cell offers insights into how the Microprocessor (MP) complex processes pri-let-7 microRNAs (miRNAs). These findings hold promise for advancing RNA-based diagnostics, particularly for diseases like cancer.
MicroRNAs are small RNA molecules that regulate gene expression. Their processing and activity are closely linked to disease, making them valuable biomarkers. The let-7 miRNA family, in particular, plays a critical role in tumor suppression, making it a focus for diagnostic research.
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Using advanced cryo-electron microscopy (cryo-EM), researchers studied how the MP complex, made up of the proteins Drosha and DGCR8, processes pri-let-7 miRNAs. Key discoveries include:
Flexibility in processing. MP can adjust to different RNA structures, ensuring accurate processing. A newly identified “flipped U with paired N” (fUN) motif is key to this adaptability.
Two processing pathways. Pri-let-7 miRNAs are divided into two classes, each processed differently. This difference may provide unique biomarkers for disease.
Enhanced accuracy. A splicing protein, SRSF3, helps MP process miRNAs more precisely by stabilizing the interaction with RNA.
The research team’s findings pave the way for new diagnostic tools; for example, disruptions in miRNA processing, such as changes in pri-let-7 forms, could serve as biomarkers for detecting disease, offering a pathway to more precise diagnostics. And by targeting structural motifs like the fUN or CNNC motif, researchers could develop specific RNA tests tailored to identify these disruptions.
Moreover, understanding the structure and function of miRNA processing could aid in monitoring the effectiveness of therapies targeting RNA pathways – leading to improved disease detection methods.
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