An armadillo-domain protein participates in a telomerase interaction network

Abstract

Arabidopsis and human ARM protein interact with telomerase. Deregulated mRNA levels of DNA repair and ribosomal protein genes in an Arabidopsis arm mutant suggest non-telomeric ARM function. The human homolog ARMC6 interacts with hTRF2. Telomerase maintains telomeres and has proposed non-telomeric functions. We previously identified interaction of the C-terminal domain of Arabidopsis telomerase reverse transcriptase (AtTERT) with an armadillo/β-catenin-like repeat (ARM) containing protein. Here we explore protein-protein interactions of the ARM protein, AtTERT domains, POT1a, TRF-like family and SMH family proteins, and the chromatin remodeling protein CHR19 using bimolecular fluorescence complementation (BiFC), yeast two-hybrid (Y2H) analysis, and co-immunoprecipitation. The ARM protein interacts with both the N- and C-terminal domains of AtTERT in different cellular compartments. ARM interacts with CHR19 and TRF-like I family proteins that also bind AtTERT directly or through interaction with POT1a. The putative human ARM homolog co-precipitates telomerase activity and interacts with hTRF2 protein in vitro. Analysis of Arabidopsis arm mutants shows no obvious changes in telomere length or telomerase activity, suggesting that ARM is not essential for telomere maintenance. The observed interactions with telomerase and Myb-like domain proteins (TRF-like family I) may therefore reflect possible non-telomeric functions. Transcript levels of several DNA repair and ribosomal genes are affected in arm mutants, and ARM, likely in association with other proteins, suppressed expression of XRCC3 and RPSAA promoter constructs in luciferase reporter assays. In conclusion, ARM can participate in non-telomeric functions of telomerase, and can also perform its own telomerase-independent functions.

The plant Pontin and Reptin homologues, RuvBL1 and RuvBL2a, colocalize with TERT and TRB proteins in vivo, and participate in telomerase biogenesis

“…Homologues of the mammalian Pontin and Reptin, named RuvBL proteins, as well as TRB proteins, might be involved in diverse processes in the plant cell. AtTRB proteins are not only components of terminal complex associated with telomeres and catalytic subunit of telomerase, AtTERT (Schrumpfová et al ., , ), but they also serve as epigenetic regulators that potentially impact the transcription status of thousands of genes as subunits of epigenetically active multiprotein complexes (Lee and Cho, ; Schrumpfová et al ., ; Zhou et al ., ; Dokládal et al ., ; Tan et al ., ). AtRuvBL1 protein has been assumed as a regulator of R genes so far and is essential in meristem development (Holt et al ., ).…”

Composition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes

“…In plants, the armadillo/β-catenin-like repeat-containing protein (ARM) or Chromatin remodeling 19 (CHR19) proteins associated with TERT may reflect the possible non-telomeric functions of telomerase [167]. ARM proteins play a role in the Wnt/β-catenin signaling pathway in humans [168], but the non-telomeric functions of plant TERT or TR remain elusive.…”

Telomeres in Plants and Humans: Not So Different, Not So Similar

“…TRB proteins are not only components of the terminal complex associated with telomeres/telomerase, but they are also associated in vivo with promoters of translation machinery genes, which mostly contain a short telomeric sequence [67]. It seems that TRB proteins serve as epigenetic regulators that potentially affect the transcription status of thousands of genes by playing a role of recruiting subunits of multiple epigenetically active multi-protein complexes [68,69,70,71,155,156]. These findings are consistent with the observations from yeast or mammals where telomeric proteins (e.g., TRF1, TRF2, and RAP1) are able to localize outside telomeric regions and regulate the transcription of genes involved in metabolism, immunity, and differentiation [157,158,159,160,161,162,163,164].…”

“…Surprisingly, no functions in telomere maintenance were found in Arabidopsis orthologues of mammalian TRF proteins (TRFL proteins) where a myb-domain of the telobox type is located C-terminally as in human TRF1 and TRF2 [165]. However, a recent study revealed protein-protein interactions between TRFL2 and TRP1, members of the TRFL family, and TERT from A. thaliana [66,69]. Plant TRFL2 and TRP1 proteins interact with armadillo/β-catenin-like repeat-containing protein (ARM).…”

“…Plant TRFL2 and TRP1 proteins interact with armadillo/β-catenin-like repeat-containing protein (ARM). ARM directly interacts with plant TERT [70] and might be involved in translation initiation or in regulation of recombination-related genes [69]. Moreover, ARM interacts with the chromatin remodeling protein CHR19 (Table 1).…”