Normal and pathological functions of mammalian retroelements

Abstract

In a recent issue of PNAS, Garen and colleagues (1) reported that the RNA transcribed from the retroelement VL30 binds to the repressor protein PSF followed by disengagement of PSF from the repressed genes and activation of transcription (1–3). The departure point for this remarkable discovery was an experiment involving retroviral-mediated transfection of the tissue factor gene into a weakly metastatic human melanoma cell line (4). Some of the transfected melanoma clones were strongly metastatic, and these were found to be cotransfected with VL30 RNA derived from the packaging cell line. In a series of elegant experiments, the Garen laboratory showed that the effect of VL30 RNA on metastasis was mediated by binding to PSF. PSF (5–6) belongs to a class of repressor proteins that contains a DNA-binding domain (DBD) and a RNA-binding domains (RBD). Formation of a complex between VL30 RNA and PSF protein reversed repression of multiple genes (as shown in Fig. 1), including proto-oncogenes and P450scc that initiates steroidogenesis (1, 3). This mechanism of reversible gene regulation does not involve mutations of either the repressor protein or repressed gene (1). Fig. 1. Mechanism of VL30 interaction with PSF. ( Left ) Gene repression when the DBD (DNA-binding domain) of PSF binds to a promoter (P). ( Right ) Derepression of the gene when VL30 RNA binds to the RBD (RNA-binding domains) of PSF and releases PSF from the …