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Robust Filtering and Noise Suppression in Intragenic miRNA-Mediated Host Regulation.


ABSTRACT: MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target messenger RNAs (mRNAs). Many human miRNAs are intragenic, located within introns of protein-coding sequence (host). Intriguingly, a percentage of intragenic miRNAs downregulate the host transcript forming an incoherent feedforward motif topology. Here, we study intragenic miRNA-mediated host gene regulation using a synthetic gene circuit stably integrated within a safe-harbor locus of human cells. When the intragenic miRNA is directed to inhibit the host transcript, we observe a reduction in reporter expression accompanied by output filtering and noise reduction. Specifically, the system operates as a filter with respect to promoter strength, with the threshold being robust to promoter strength and measurement time. Additionally, the intragenic miRNA regulation reduces expression noise compared to splicing-alone architecture. Our results provide a new insight into miRNA-mediated gene expression, with direct implications to gene therapy and synthetic biology applications.

SUBMITTER: Kang T 

PROVIDER: S-EPMC7554026 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Robust Filtering and Noise Suppression in Intragenic miRNA-Mediated Host Regulation.

Kang Taek T   Quarton Tyler T   Nowak Chance M CM   Ehrhardt Kristina K   Singh Abhyudai A   Li Yi Y   Bleris Leonidas L  

iScience 20200921 10


MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to target messenger RNAs (mRNAs). Many human miRNAs are intragenic, located within introns of protein-coding sequence (host). Intriguingly, a percentage of intragenic miRNAs downregulate the host transcript forming an incoherent feedforward motif topology. Here, we study intragenic miRNA-mediated host gene regulation using a synthetic gene circuit stably integrated within a safe-  ...[more]

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