Euplotes telomerase contains an La motif protein produced by apparent translational frameshifting

Telomerase is the ribonucleoprotein enzyme responsible for the replication of chromosome ends in most eukaryotes. In the ciliate Euplotes aediculatus, the protein p43 biochemically co-purifies with active telomerase and appea rs to be stoichiometric with both the RNA and the catalytic protein subunit of this telomerase complex. Here we describe cloning of the gene for p43 a nd present evidence that it is an authentic component of the telomerase hol oenzyme. Comparison of the nucleotide sequence of the cloned gene with pept ide sequences of the protein suggests that production of full-length p43 re lies on a programmed ribosomal frameshift, an extremely rare translational mechanism. Anti-p43 antibodies immunodeplete telomerase RNA and telomerase activity from E.aediculatus nuclear extracts, indicating that the vast majo rity of mature telomerase complexes in the cell are associated with p43. Th e sequence of p43 reveals similarity to the La autoantigen, an RNA-binding protein involved in maturation of RNA polymerase III transcripts, and recom binant p43 binds telomerase RNA in vitro. By analogy to other La proteins, p43 may function in chaperoning the assembly and/or facilitating nuclear re tention of telomerase.