Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

Abstract

We describe a mechanism of gene regulation involving formation of a complex between PSF protein and mouse VL30 (mVL30) retrotransposon RNA. PSF represses transcription of the insulin-like growth factor 1 (IGF1)-inducible gene P450scc by binding to an insulin-like growth factor response element (IGFRE) motif in the gene. The complex with mVL30 RNA releases PSF, allowing transcription to proceed. Retrovirally mediated transmission of mVL30 RNA to human tumor cells induced several genes, including oncogenes, which also are induced by IGF1, and promoted metastasis. In mice, steroid synthesis is activated in steroidogenic cells by pituitary hormones, which concomitantly induce transcription of mVL30 RNA in the cells. We showed that steroid synthesis could also be activated in mouse steroidogenic adrenal cells by transfection with cDNA encoding either mVL30 RNA tracts that form a complex with PSF or a small interfering RNA (siRNA) that degrades PSF transcripts. These results suggest that mVL30 RNA regulates steroidogenesis, and possibly other physiological processes of mice, by complex formation with PSF. Retrotransposons such as mVL30 apparently evolved not only as "junk" DNA but also as transcriptionally active noncoding DNA that acquired physiological and pathological functions.