Translational repression of cyclin D3 by a stable G-quadruplex in its 5′ UTR: implications for cell cycle regulation

摘要: cyclin D3 (CCND3) is one of the three D-type cyclins that regulate G1/S phase transition cell cycle. Expression CCND3 observed in nearly all proliferating cells; however, presence high levels has been linked to a poor prognosis for several types cancer. Therefore, further mechanistic studies on regulation expression are urgently needed provide therapeutic implications. In this study, we report conserved RNA G-quadruplex-forming sequence (hereafter CRQ), located 5′ UTR mammalian mRNA, able fold into an extremely stable, intramolecular, parallel G-quadruplex vitro. The CRQ dramatically reduces activity reporter gene human lines, but it little impact its mRNA level, indicating translational repression. Moreover, natural context inhibits translation CCND3. Disruption structure by G/U-mutation or deletion results elevated C...