The long terminal repeat of an endogenous retrovirus induces alternative splicing and encodes an additional carboxy-terminal sequence in the human leptin receptor

The evolution of mammalian protein structure and regulation, specifically t ranscriptional and posttranscriptional regulation, may include among its to ols the use of abundant retroviral long terminal repeats (LTRs). In particu lar, LTRs may be turned into switches for alternative splicing. This type o f regulatory pathway is illustrated by the alternative splicing in the huma n leptin receptor (OBR). The human leptin receptor is involved in the contr ol of important biological processes including energy expenditure, producti on of sex hormones, and activation of hemopoietic cells. OBRa and OBRb are the two major, alternatively spliced forms of the leptin receptor, called t he "short form" and the "long form," respectively. We report that the OBRa short form is the result of a double splicing event which occurs within the LTR of the endogenous retrovirus HERV-K. Working as a switch of alternativ e splicing, this LTR also encodes the terminal 67 amino acid residues in OB Ra. We suggest the possibility of transcriptional and posttranscriptional r egulation of OBR expression by steroids that bind the LTR.