Breaking new ground: the emergence of non‐canonical functions for telomerase subunits in plants

Abstract

The telomere complex is highly conserved and essential for genome integrity. Recent studies reveal that core constituents of telomerase and the telomere cap can function off the telomere to promote DNA repair and regulate various metabolic processes in the cytoplasm. We are investigating how two telomere‐related factors in Arabidopsis contribute to genome stability through non‐canonical pathways. Protection of telomeres 1 (POT1) encodes a telomere binding protein implicated in chromosome end protection and telomerase regulation. Although most organisms harbor a single POT1 gene, in the few lineages where the POT1 family has expanded the duplicate genes evolved distinct functions. Arabidopsis thaliana provides an extreme example of divergence wherein the POT1a paralog retains the ancestral function of stimulating telomerase activity, while the POT1b paralog localizes to the cytoplasm and plays no direct role in telomere biology. Plants deficient in POT1b are hypersensitive to genotoxic stress as a result of environmental insult or intrinsic metabolic stress, and produce fewer, lower quality seeds. Notably, POT1b transcription is not regulated by genotoxic stress, but instead is developmentally regulated and concentrated in reproductive tissues. These findings indicate that POT1b evolved to serve a protective role for the genome, increasing plant fitness.Arabidopsis also encodes a non‐canonical telomerase‐associated lncRNA called TER2. TER2 is a brand‐new gene unique to A. thaliana. TER2 is induced in response to DNA double‐strand breaks and its induction causes a rapid decrease in telomerase activity, likely to avert inappropriate telomerase action at sites of DNA damage. Unexpectedly, we found that plants doubly deficient in TER2 and POT1a exhibit a highly accelerated rate of telomere shortening that triggers massive genome instability and gross morphological defects earlier than in plants completely lacking telomerase. Thus, TER2 works in concert with the conventional telomerase enzyme to promote genome stability and telomere replication. Strikingly, like POT1b, TER2 can also be found in the cytoplasm and co‐expresses with POT1b in reproductive organs and seeds. As with pot1b mutants, plants lacking TER2 are hypersensitive to genotoxic stress and have reduced fitness. Finally, biochemical experiments indicate that POT1b physically interacts with TER2. Altogether, these data suggest that POT1b and TER2 are co‐evolving a novel protective mechanism for the plant genome.Support or Funding InformationThis research was supported by grants from NIH (R01‐GM065383) and NSF (MCB 1517817) to D.S.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.