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

Abstract

Summary Post-transcriptional 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 catalogue of functional regulatory elements embedded in 3’-untranslated regions (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, non-coding 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 post-transcriptional fates of human transcripts. This combined experimental/computational strategy can be used to systematically characterize the vast landscape of post-transcriptional regulatory elements controlling physiological and pathological cellular state transitions.

RNA–protein interaction detection in living cells

“…Tavazoie et al . 29 recently demonstrated decreased levels of RNA transcripts bearing SM1v1 motifs in breast cancer patients with advanced tumors. However, putative binding factors to the SM1v1 motif have not been characterized.…”

Rapid Proteasomal Degradation of Posttranscriptional Regulators of the TIS11/Tristetraprolin Family Is Induced by an Intrinsically Unstructured Region Independently of Ubiquitination

“…cis regulatory elements, often located in the 3= untranslated region (UTR), influence the localization, translation, and degradation status of mRNAs (1,2) by binding trans-acting microRNAs or RNA-binding proteins (see references 3 and 4 for reviews). AU-rich elements (AREs) are the most common cis-acting determinants found in metazoan mRNAs (5,6).…”

Cancer whole-genome sequencing: present and future

“…76 Synonymous mutations in coding regions and intronic regions can alter exonic motifs that regulate splicing and the functions of cancer-related genes. 31 There are also many fusion events detected by RNA-Seq and most of them are caused by genomic rearrangement. [48][49][50][51] Some SVs affecting non-coding regions can also change the expression of nearby genes owing to changes of regulatory elements and chromatin structures.…”

“…28,29 In addition to these ncRNAs, the initial transcripts of protein-coding genes usually contain extensive non-coding sequences, in the form of introns, 5ʹ UTRs and 3ʹ UTRs, which are also involved with the regulation of RNA transcription, RNA splicing and protein translational processes. 30,31 Mutations in 3ʹ UTR may tend to occur in cancer driver genes 32 and are likely to control RNA stability and protein translation through microRNA binding. 30,31 Furthermore, intergenic regions are likely to have many different regulatory element sequences, which are crucial to regulating Figure 2.…”

“…30,31 Mutations in 3ʹ UTR may tend to occur in cancer driver genes 32 and are likely to control RNA stability and protein translation through microRNA binding. 30,31 Furthermore, intergenic regions are likely to have many different regulatory element sequences, which are crucial to regulating Figure 2. A representative set of analysis tools for cancer WGS data.…”