Translational repression by the cis-acting element of structure-anchored repression (CAESAR) of human ctgf/ccn2 mRNA.
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.
Kubota
Satoshi
S
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine and Dentistry, Japan.
Mukudai
Yoshiki
Y
Moritani
Norifumi H
NH
Nakao
Kyouji
K
Kawata
Kazumi
K
Takigawa
Masaharu
M
D020413:3' Untranslated Regions; D021581:Active Transport, Cell Nucleus; D000818:Animals; D020029:Base Pairing; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D055513:Connective Tissue Growth Factor; D015536:Down-Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
D020413:3' Untranslated Regions; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D008156:Luciferases