A FUNCTIONAL TELOMERASE RNA SWAP IN-VIVO REVEALS THE IMPORTANCE OF NONTEMPLATE RNA DOMAINS

The ribonucleoprotein (RNP) enzyme telomerase is required for replicat ion of eukaryotic chromosomal termini. The RNA moiety of telomerase is essential for enzyme function and provides the template for telomeric DNA synthesis, However, the roles of its nontemplate domains have not been explored, Here we demonstrate that a novel interspecies telomera se RNA swap in vivo creates a functional but aberrant telomerase. Telo merase RNA from the ciliate Glaucoma chattoni was expressed in Tetrahy mena thermophila cells. The telomerase RNAs from these two species hav e almost superimposable secondary structures, The template region base sequence is identical in the two RNAs, but elsewhere their sequences differ by 49%. This hybrid telomerase RNP was enzymatically active but added only short stretches of telomeric repeat tracts in vivo and in vitro, This new enzyme also had a strong, aberrant DNA cleavage activi ty in vitro. Thus, molecular interactions in the RNP involving nontemp late RNA domains affect specific aspects of telomerase enzyme function , raising the possibility that they may regulate telomerase activity.