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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Translational repression by the cis-acting element of structure-anchored repression (CAESAR) of human ctgf/ccn2 mRNA
Satoshi Kubota1, Yoshiki Mukudai, Norifumi H Moritani
1Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, Japan.
Abstract:
The cis-acting element of structure-anchored repression (CAESAR) is a post-transcriptional regulatory element of gene expression, which is located in the 3'-untranslated region (UTR) of the human ccn2 gene (ctgf/ccn2). In this report, the repression mechanism of CAESAR, as well as the structural requirement, was investigated. Removal of minor stem-loops from CAESAR resulted in proportional attenuation of the repressive function, whereas removal of the single bulge or modification of primary nucleotide sequence did not affect its functionality. In light of functional mechanism, CAESAR exerted no significant effects on stability or nuclear export of the cis-linked mRNA. However, this element significantly interfered with the association of such mRNA on ribosome and slowed down the translation process thereafter in vitro. A translation repression mechanism by RNA secondary structure to determine the basal ctgf/ccn2 expression level was uncovered herein.
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