title: An alternative telomerase RNA in Arabidopsis modulates enzyme activity in response to DNA damage.
abstract: Telomerase replenishes telomere tracts by reiteratively copying its RNA template, TER. Unlike other model organisms, Arabidopsis thaliana harbors two divergent TER genes. However, only TER1 is required for telomere maintenance. Here we examine the function of TER2. We show that TER2 is spliced and its 3' end is truncated in vivo to generate a third TER isoform, TER2(S). TERT preferentially associates with TER2 > TER1 > TER2(S). Moreover, TER2 and TER2(S) assemble with Ku and POT1b (protection of telomeres), forming RNP (ribonucleoprotein) complexes distinct from TER1 RNP. Plants null for TER2 display increased telomerase enzyme activity, while TER2 overexpression inhibits telomere synthesis from TER1 and leads to telomere shortening. These findings argue that TER2 negatively regulates telomerase by sequestering TERT in a nonproductive RNP complex. Introduction of DNA double-strand breaks by zeocin leads to an immediate and specific spike in TER2 and a concomitant decrease in telomerase enzyme activity. This response is not triggered by replication stress or telomere dysfunction and is abrogated in ter2 mutants. We conclude that Arabidopsis telomerase is modulated by TER2, a novel DNA damage-induced noncoding RNA that works in concert with the canonical TER to promote genome integrity.
authors.affiliation: Department of Biochemistry and Biophysics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cifuentes-Rojas
authors.forename: Andrew D L
authors.initials: AD
authors.lastname: Nelson
authors.forename: Kara A
authors.initials: KA
authors.lastname: Boltz
authors.forename: Kalpana
authors.initials: K
authors.lastname: Kannan
authors.forename: Xintao
authors.initials: X
authors.lastname: She
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Shippen
mesh_terms: D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics*; D029681:Arabidopsis Proteins / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics*; D004789:Enzyme Activation; D018506:Gene Expression Regulation, Plant / Q000235:genetics; D012313:RNA / Q000235:genetics* / Q000378:metabolism*; D026721:RNA 3' End Processing; D012326:RNA Splicing; D012261:Ribonucleoproteins / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000235:genetics
chemical_list: D029681:Arabidopsis Proteins; D012261:Ribonucleoproteins; C422952:telomerase RNA; D012313:RNA; C528255:TERT protein, Arabidopsis; D019098:Telomerase