28S ribosomal RNA (28S rRNA) (28S rRNA)

The 28S ribosomal RNA (28S rRNA) is a fundamental structural and catalytic component of the eukaryotic 60S ribosomal subunit, essential for the process of translation and peptide bond formation (Endo et al., 1988). It is the primary molecular target for mistletoe lectin A-chain (ML-A), a Type II ribosome-inactivating protein (RIP) derived from the Viscum album plant (Büssing, 2000). ML-A exhibits potent RNA N-glycosidase activity, specifically targeting the highly conserved sarcin/ricin loop (SRL) of the 28S rRNA and removing a single adenine residue at position A4324 (UniProt P06750). This site-specific depurination prevents the binding of elongation factors EF-1 and EF-2, leading to an irreversible halt in protein synthesis and the induction of the ribotoxic stress response. In clinical oncology, mistletoe extracts containing these lectins, such as Iscador and Helixor, are utilized as complementary therapies to induce apoptosis in malignant cells and stimulate the host immune system (Kienle & Kiene, 2010). The interaction between ML-A and the ribosome triggers multiple signaling cascades, including the activation of JNK and p38 mitogen-activated protein kinases, which further promote programmed cell death. While the ribosome is a ubiquitous target, the therapeutic window of mistletoe lectins is managed through specific dosing and the cell-binding properties of the associated B-chain, which facilitates entry into target cells.

Other names

28S rRNALarge ribosomal subunitSarcin/ricin loopSRL60S ribosomal subunitRibosome

Mistletoe lectin A-chain (ML-A) acts as an RNA N-glycosidase that specifically depurinates the A4324 residue of the 28S ribosomal RNA within the sarcin/ricin loop. This modification prevents the binding of elongation factors, thereby irreversibly inhibiting protein synthesis and triggering apoptosis through the ribotoxic stress response (Endo et al., 1988; Stirpe, 2004).