The BCL-2 5' untranslated region contains an RNA G-quadruplex-forming motif that modulates protein expression.
The BCL-2 gene encodes a 25 kDa membrane protein that plays critical roles in the control of apoptosis. The regulation of BCL-2 gene expression is highly complex and occurs both transcriptionally and posttranscriptionally. In particular, the 5' upstream region of BCL-2 contains a number of elements that control its expression. We have identified a highly conserved 25-nucleotide G-rich sequence (BCL2Q), with potential to fold into a RNA G-quadruplex structure, located 42 nucleotides upstream of the translation start site of human BCL-2. In this study, we used a series of biophysical experiments to show that the BCL2Q sequence folds into a stable RNA G-quadruplex in vitro, and we conducted functional luciferase reporter-based assays, in a cell-free lysate and in three types of human cell lines, to demonstrate that the BCL2Q sequence modulates protein expression in the context of the 493-nucleotide native 5' untranslated region of BCL-2.
Shahid
Ramla
R
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Bugaut
Anthony
A
Balasubramanian
Shankar
S
D020121:5' Untranslated Regions; D020816:Amino Acid Motifs / Q000235:genetics; D001483:Base Sequence; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D019254:Genes, bcl-2; D006801:Humans; D017434:Protein Structure, Tertiary / Q000235:genetics
D020121:5' Untranslated Regions