RNA structural analysis of the MYC mRNA reveals conserved motifs that affect gene expression

• DOI: 10.1371/journal.pone.0213758
• Publication Date: 2019-06-17T17:25:55Z
• Authors: Collin A. O’Leary; Ryan J. Andrews; Van S. Tompkins; Jonathan L. Chen; Jessica L. Childs...; Matthew D. Disney; Walter N. Moss
• Keywords: Conserved sequence; Pseudoknot

The MYC gene encodes a human transcription factor and proto-oncogene that is dysregulated in over half of all known cancers. To better understand potential post-transcriptional regulatory features affecting expression, we analyzed secondary structures the mRNA using program optimized for finding small locally-folded motifs with high propensity function. This was accomplished by calculating folding metrics across sequence sliding analysis window generating unique consensus base pairing models weighted their lower-than-random predicted energy. A series 30 were identified, primarily 5' 3' untranslated regions, which show evidence structural conservation compensating mutations vertebrate homologs. able to recapitulate elements found within an internal ribosomal entry site, as well discover novel element UTR unusually stable conserved. motif shown affect potentially via modulation miRNA target accessibility or other trans-regulatory factors. In addition providing basic insights into mechanisms regulate this study provides numerous, druggable RNA targets gene, considered “undruggable” at protein level.