Telomerase RNA is more than a DNA template

Abstract

The addition of telomeric DNA to chromosome ends is an essential cellular activity that compensates for the loss of genomic DNA that is due to the inability of the conventional DNA replication apparatus to duplicate the entire chromosome. The telomerase reverse transcriptase and its associated RNA bind to the very end of the telomere via a sequence in the RNA and specific protein-protein interactions. Telomerase RNA also provides the template for addition of new telomeric repeats by the reverse-transcriptase protein subunit. In addition to the template, there are 3 other conserved regions in telomerase RNA that are essential for normal telomerase activity. Here we briefly review the conserved core regions of telomerase RNA and then focus on a recent study in fission yeast that determined the function of another conserved region in telomerase RNA called the Stem Terminus Element (STE). (1) The STE is distant from the templating core of telomerase in both the linear and RNA secondary structure, but, nonetheless, affects the fidelity of telomere sequence addition and, in turn, the ability of telomere binding proteins to bind and protect chromosome ends. We will discuss possible mechanisms of STE action and the suitability of the STE as an anti-cancer target.

TERRA RNA Antagonizes ATRX and Protects Telomeres

“…Interestingly, RNA-seq and RT-qPCR revealed a 2-fold increase in expression of the telomerase RNA component, Terc (Webb and Zakian, 2016), in TERRA-depleted ES cells (Fig. 6A,B).…”

TERribly Difficult: Searching for Telomerase RNAs in Saccharomycetes

“…Other major features are the template, the pseudoknot region, the template boundary element (TBE) and the three-way junction (TWJ). Adapted from [8].…”

New perspectives on telomerase RNA structure and function

“…Since this time, the intriguing properties of the telomerase RNP enzyme, together with the potential biomedical significance of telomerase‐based therapeutics, has fueled tremendous efforts to better understand the structure, function, and regulation of this fascinating enzyme. There are many excellent review articles that cover in detail recent advances in telomerase structure and biogenesis, as well as evolutionary origins of the telomerase complex . Therefore, rather than provide a comprehensive review of the telomerase literature, we have elected to highlight recently reported discoveries from the three best‐studied telomerase systems: ciliates, yeasts, and vertebrates.…”

“…There are many excellent review articles that cover in detail recent advances in telomerase structure and biogenesis, as well as evolutionary origins of the telomerase complex. 2,8,[26][27][28][29][30][31][32][33][34] Therefore, rather than provide a comprehensive review of the telomerase literature, we have elected to highlight recently reported discoveries from the three best-studied telomerase systems: ciliates, yeasts, and vertebrates. Specifically, we have chosen recent findings that have changed our view of the how RNA contributes to the unique functional properties of the telomerase complex.…”