Bip internal ribosome entry site (IRES)

A BiP internal ribosome entry site (IRES) is a specific RNA sequence found within the 5' untranslated region (5' UTR) of certain mRNA molecules that allows for cap-independent translation initiation. Unlike typical eukaryotic translation, which relies on the 5' cap structure to recruit ribosomes, the BiP IRES enables ribosomes to directly bind to the mRNA near the start codon (typically AUG) and initiate translation.

The BiP IRES is named after its initial discovery in the mRNA encoding Binding Immunoglobulin Protein (BiP), also known as GRP78 (Glucose-Regulated Protein 78), a major endoplasmic reticulum (ER) chaperone. It plays a critical role in allowing BiP expression to continue or even increase under conditions of ER stress, when cap-dependent translation is often globally reduced. This selective translation is essential for maintaining ER homeostasis and cellular survival.

Structurally, BiP IRES elements form complex secondary and tertiary structures that can directly interact with ribosomes and associated initiation factors. These structures vary in sequence and complexity, but they share the common function of facilitating ribosome recruitment in a cap-independent manner. The BiP IRES specifically allows for translation of BiP during periods of stress, bypassing the normal requirement for the 5' cap that is needed for the translation of most cellular proteins. This is crucial in the Unfolded Protein Response (UPR), a signaling pathway activated when unfolded proteins accumulate in the ER lumen. The BiP IRES, therefore, is a crucial element involved in cellular stress response pathways.