Systematic Identification of Regulatory Elements in Conserved 3′ UTRs of Human Transcripts

•Functional characterization of short, conserved 3′ UTR sequences•Discovery of linear and structural RNA motifs controlling gene expression•Validation of the repressive regulatory effect of C3U-SM1, a structural RNA motif

SummaryPosttranscriptional regulatory programs governing diverse aspects of RNA biology remain largely uncharacterized. Understanding the functional roles of RNA cis-regulatory elements is essential for decoding complex programs that underlie the dynamic regulation of transcript stability, splicing, localization, and translation. Here, we describe a combined experimental/computational technology to reveal a catalog of functional regulatory elements embedded in 3′ UTRs of human transcripts. We used a bidirectional reporter system coupled with flow cytometry and high-throughput sequencing to measure the effect of short, noncoding, vertebrate-conserved RNA sequences on transcript stability and translation. Information-theoretic motif analysis of the resulting sequence-to-gene-expression mapping revealed linear and structural RNA cis-regulatory elements that positively and negatively modulate the posttranscriptional fates of human transcripts. This combined experimental/computational strategy can be used to systematically characterize the vast landscape of posttranscriptional regulatory elements controlling physiological and pathological cellular state transitions.

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