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.

Graphical AbstractFigure optionsDownload as PowerPoint slide