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

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 the model social amoeba Dictyostelium discoideum, we show that the protein encoded by tert has telomerase-like motifs, and regulates, non-canonically, important developmental processes. Expression levels of wild-type (WT) tert were biphasic, peaking at 8 and 12 h post-starvation, aligning with developmental events, such as the initiation of streaming (~7 h) and mound formation (~10 h). In tert KO mutants, however, aggregation was delayed until 16 h. Large, irregular streams formed, then broke up, forming small mounds. The mound-size defect was not induced when a KO mutant of countin (a master size-regulating gene) was treated with TERT inhibitors, but anti-countin antibodies did rescue size in the tert KO. Although, conditioned medium (CM) from countin mutants failed to rescue size in ...

端粒酶（telomerase），尤其是其主要亚基——端粒酶逆转录酶（TERT），可在真核染色体复制过程中阻止DNA降解，但同时也存在尚未阐明的非经典功能。本研究以模式社会变形虫盘基网柄菌（Dictyostelium discoideum）为实验模型，证实tert基因编码的蛋白带有端粒酶样基序，并以非经典方式调控关键发育进程。野生型（wild-type，WT）tert的表达呈双相模式，在饥饿处理后8小时与12小时达到表达峰值，这与细胞发育事件高度契合，例如流聚起始（约7小时）与菌团形成（约10小时）。然而，在tert基因敲除（KO）突变体中，细胞聚集过程延迟至16小时才启动，形成大型不规则流聚体后发生解离，最终形成小型菌团。当用TERT抑制剂处理countin（一种主控细胞尺寸调控的基因）的敲除突变体时，并未诱导出现菌团尺寸异常表型；但抗countin抗体可挽救tert敲除突变体的尺寸缺陷。尽管countin突变体的条件培养基（conditioned medium，CM）无法挽救尺寸异常……