FGF-1 internal ribosome entry site (IRES)

An FGF-1 internal ribosome entry site (IRES) is a specific RNA sequence found within the 5' untranslated region (5' UTR) of the mRNA encoding fibroblast growth factor 1 (FGF-1). Unlike the canonical cap-dependent translation initiation, which relies on the 5' cap structure of mRNA to recruit ribosomes, an IRES element allows for cap-independent translation initiation. This means that the ribosome can bind directly to the mRNA at the IRES, bypassing the need for the initiation factors that normally bind to the 5' cap.

The FGF-1 IRES is of particular interest because FGF-1 lacks a signal sequence and is not typically secreted via the classical endoplasmic reticulum (ER)-Golgi pathway. Instead, it relies on IRES-mediated translation and a non-classical export pathway for its release from the cell. Under conditions of cellular stress, such as hypoxia or heat shock, cap-dependent translation is often inhibited. The FGF-1 IRES, however, can remain active, allowing for continued synthesis of FGF-1. This suggests a role for IRES-mediated translation in ensuring the production of FGF-1 under stressful conditions where it may be needed for cell survival and repair.

The exact structure and mechanism of action of the FGF-1 IRES are complex and involve specific RNA secondary structures and interactions with various RNA-binding proteins. These proteins facilitate ribosome recruitment and initiation of translation at the AUG start codon located downstream of the IRES element. Understanding the intricacies of the FGF-1 IRES can provide insights into the regulation of FGF-1 expression and its role in various physiological and pathological processes, including angiogenesis, wound healing, and tumor development.