MYC internal ribosome entry site (MYC IRES) (MYC IRES)

The MYC internal ribosome entry site (MYC IRES) is a highly structured RNA element located within the 5' untranslated region (UTR) of the MYC (c-Myc) mRNA (Stoneley et al., 2000, Nucleic Acids Research). It facilitates cap-independent translation initiation, allowing for the continued synthesis of the MYC oncoprotein even when global cap-dependent translation is suppressed, such as during cellular stress, hypoxia, or apoptosis (Spriggs et al., 2008, Genes & Development). This mechanism is crucial for the survival and proliferation of cancer cells within the often-hostile tumor microenvironment, where MYC acts as a master regulator of cell growth and metabolism (Dang, 2012, Cell). Because MYC is frequently overexpressed in a wide array of human malignancies, the MYC IRES represents an attractive therapeutic target for reducing oncogenic protein levels (Boussemart et al., 2014, Nature). Small molecules like CMLD010506 and various antisense oligonucleotides are being explored to disrupt the IRES structure or its interaction with IRES-transacting factors (ITAFs) such as PTBP1 and hnRNP K (Evans et al., 2003, Molecular and Cellular Biology; Hart et al., 2014, PNAS). However, targeting this element poses significant challenges, including the potential for off-target effects on other essential IRES-containing mRNAs and the risk of systemic toxicity due to MYC's critical role in normal tissue homeostasis and regeneration (Soucek et al., 2008, Nature).

Other names

c-Myc IRESMYC 5' UTR IRESInternal ribosome entry site of MYC mRNA

Inhibition of IRES-mediated translation initiation by disrupting RNA secondary structure or blocking the binding of IRES-transacting factors (ITAFs).