The activity of S. pombe LTR retrotransposons is activated in response to rapamycin

Long terminal repeat (LTR) retrotransposons are mobile genetic elements that are present in the genomes of most eukaryotes. They are closely related to retroviruses and mobilize through an RNA intermediate. The uncontrolled mobilization of retrotransposons is potentially harmful to the integrity of the genome and so the activity of these elements is subjected to strict host cell controls. We are using the fission yeast, Schizosaccharomyces pombe to study the signalling pathways that regulate the activity ofLTR retrotransposons. We have found that the expression and mobilization of the Tf2 LTR retrotransposons is activated in response to exposure to the immunosuppressant drug rapamycin. Rapamycin binds to the conserved FKBP12 protein (called Fkh1 in S. pombe) and the resulting FKBP12-rapamycin complex inhibits the kinase activity of the conserved the TORC1 complex. This suggests that Tf2 activity is under the control of the TORC1 signalling network which is a master regulator of cellular responses to nutrient and energy availability. However, the inhibition of TORC1 activity using a tor2 temperature sensitive allele or a direct chemical inhibitor (Torin) did not activate either the expression or mobilization of Tf2 elements. Therefore, rapamycin may be controlling Tf2 activity via a TORC1-independent pathway. We are currently defining this pathway and find that it is dependent upon the FKBP12 protein, Fkh1 and the Forkhead transcription factor, Fhl1.