Authors:

Nicholas M Hiers

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About Paper:

Fibroblasts MicroRNAs (miRNAs) are small, approximately 22 nucleotides long, non-coding RNAs that regulate gene expression post-transcriptionally across various eukaryotic lineages. MiRNAs primarily interact with mRNAs to reduce their expression through miRNA-directed target degradation, influencing developmental processes and diseases. While miRNA's role in regulating mRNA is well known, how miRNAs are regulated within cells is less clear. Recently a mechanism suggests that some RNAs can "trigger" specific miRNAs' degradation in a process called target-directed miRNA degradation (TDMD). This occurs when trigger RNAs base pairs with both the miRNA's 5' and 3' regions, leading to a conformational change that facilitates recognition by the ZSWIM8 ubiquitin ligase. This results in the Argonaute (AGO) protein's polyubiquitination, marking it for 26S proteasome degradation, thereby exposing the miRNA to cytosolic ribonucleases. In this study, we explore potential trigger RNAs for miRNA degradation, utilizing CRISPR-Cas9 to knock out triggers identified in Mouse Embryonic Fibroblast cells. Upon loss of a bonafide trigger, the abundance of the miRNAs regulated by that trigger should increase. We therefore utilize northern blotting and small RNA sequencing to identify which miRNAs are sensitive to the trigger depletion. In essence, this discovery would unveil new miRNA pathways and potentially aid in cancer therapy. 437

Source:

University of Florida / 2024

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Co-authors:

Nicholas M Hiers