A telomerase with novel non-canonical roles: TERT controls cellular aggregation and tissue size in Dictyostelium

• DOI: 10.1371/journal.pgen.1008188
• Publication Date: 2019-06-25T17:27:19Z
• Authors: Nasna Nassir; Geoffrey J. Hyde; Ramamurthy Baskar
• Keywords: Wild type

Telomerase, particularly its main subunit, the reverse transcriptase, TERT, prevents DNA erosion during eukaryotic chromosomal replication, but also has poorly understood non-canonical functions. Here, in model social amoeba Dictyostelium discoideum, we show that protein encoded by tert telomerase-like motifs, and regulates, non-canonically, important developmental processes. Expression levels of wild-type (WT) were biphasic, peaking at 8 12 h post-starvation, aligning with events, such as initiation streaming (~7 h) mound formation (~10 h). In KO mutants, however, aggregation was delayed until 16 h. Large, irregular streams formed, then broke up, forming small mounds. The mound-size defect not induced when a mutant countin (a master size-regulating gene) treated TERT inhibitors, anti-countin antibodies did rescue size KO. Although, conditioned medium (CM) from mutants failed to KO, CM rescued phenotype. These additional observations indicate acts upstream smlA/countin: (i) observed expression smlA countin, being respectively lower higher (than WT) KO; (ii) known size-regulation intermediates, glucose (low) adenosine (high), mutant, defect's supplemented or adenosine-antagonist, caffeine; (iii) induction WT inhibitors. KO's other defects (delayed aggregation, streaming) associated changes cAMP-regulated processes (e.g. chemotaxis, cAMP pulsing) their regulatory factors cAMP; acaA, carA expression). Overexpression these (and size), restored single signaling centre. Our results novel, ways, regulating key events Dictyostelium.