Stability of RNA quadruplex in open reading frame determines proteolysis of human estrogen receptor alpha

作者：Endoh Tamaki; Kawasaki Yu; Sugimoto Naoki^*

来源：Nucleic Acids Research, 2013, 41(12): 6222-6231.

DOI：10.1093/nar/gkt286

mRNAs encodes not only information that determines amino acid sequences but also additional layers of information that regulate the translational processes. Notably, translational halt at specific position caused by rare codons or stable RNA structures is one of the potential factors regulating the protein expressions and structures. In this study, a quadruplex-forming potential (QFP) sequence derived from an open reading frame of human estrogen receptor alpha (hER alpha) mRNA was revealed to form parallel G-quadruplex and halt the translation elongation in vitro. Moreover, when the full-length hER alpha and variants containing synonymous mutations in the QFP sequence were expressed in cells, translation products cleaved at specific site were observed in quantities dependent on the thermodynamic stability of the G-quadruplexes. These results suggest that the G-quadruplex formation in the coding region of the hER alpha mRNA impacts folding and proteolysis of hER alpha protein by slowing down or temporarily stalling the translation elongation.

• 出版日期2013-7