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Effects of genomic disruption of a guanine quadruplex in the 5′ UTR of the Bcl‐2 mRNA in melanoma cells
Author(s) -
Serikawa Tatsuo,
Eberle Jürgen,
Kurreck Jens
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12855
Subject(s) - messenger rna , g quadruplex , translation (biology) , untranslated region , transfection , microrna , three prime untranslated region , microbiology and biotechnology , apoptosis , rna , chemistry , biology , gene , dna , biochemistry
G‐quadruplex structures in the 5′ UTR of mRNA s have been shown to suppress translation. However, all experiments published so far made use of artificial reporter systems. Here, we investigate for the first time the biological effects of the genomic disruption of a G‐quadruplex by CRISPR /Cas9. In melanoma cells lacking the G‐quadruplex‐forming sequence in the mRNA of the apoptosis inhibitor Bcl‐2, the protein level of Bcl‐2 remains virtually unchanged. Consequently, sensitivity to an inducer of apoptosis is not reduced. Thus, it is likely that the inhibitory effects of G‐quadruplexes observed to date were more pronounced due to the use of the strong overexpression in transfection experiments, whereas G‐quadruplexes in endogenous mRNA s, expressed at moderate levels, are widely resolved by cellular RNA helicases.