The solution structure of an essential stem-loop of XXXX telomerase RNA.

@entity1 @entity2036 @entity1391 @entity375 @entity2215
The ribonucleoprotein enzyme telomerase maintains chromosome ends in most eukaryotes and is critical for a cell's genetic stability and its proliferative viability. All telomerases contain a catalytic protein component homologous to viral reverse transcriptases ( @entity2215 ) and an RNA (TR) that provides the template sequence as well as a scaffold for ribonucleoprotein assembly. Vertebrate telomerase RNAs have three essential domains: the template, activation and stability domains. Here we report the NMR structure of an essential RNA element derived from the @entity1 telomerase RNA activation domain. The sequence forms a stem-loop structure stabilized by a GU wobble pair formed by two of the five unpaired residues capping a short double helical region. The remaining three loop residues are in a well-defined conformation and form @entity1391 -base stacking interactions reminiscent of other RNA loop structures. Mutations of these unpaired @entity2036 abolish enzymatic activity. The structure rationalizes a number of biochemical observations, and allows us to propose how the loop may function in the telomerase catalytic cycle. The pre-formed structure of the loop exposes the bases of these three essential @entity2036 and positions them to interact with other RNA sequences within TR, with the reverse transcriptase or with the newly synthesized telomeric DNA strand. The functional role of this stem-loop appears to be conserved in even distantly related organisms such as @entity375 and ciliates.
