A role for a novel ‘trans-pseudoknot’ RNA–RNA interaction in the functional dimerization of human telomerase

Abstract

The integral RNA (hTER) of the human telomerase ribonucleoprotein has a conserved secondary structure that contains a potential pseudoknot. Here we examine the role of an intermolecular hTER–hTER interaction in the previously reported functional dimerization of telomerase. We provide evidence that the two conserved, complementary sequences of one stem of the hTER pseudoknot domain can pair intermolecularly in vitro, and that formation of this stem as part of a novel “trans-pseudoknot” is required for telomerase to be active in its dimeric form. Such RNA–RNA interaction mirrors a known property of retroviral reverse transcriptases, which use homodimeric viral genomic RNA substrates.