Abstract
The planarian flatworm is an emerging model that is useful for studying homeostasis and regeneration due to its unique adult stem cells (ASCs). Previously, planaria were found to share mammalian TTAGGG chromosome ends and telomerases; however, their telomere protection proteins have not yet been identified. In Schmidtea mediterranea, we identified a homologue of the human protection of telomeres 1 (POT1) with an OB-fold (SmedOB1). SmedOB1 is evolutionarily conserved among species and is ubiquitously expressed throughout the whole body. Feeding with SmedOB1 double-stranded RNAs (dsRNAs) led to homeostasis abnormalities in the head and pharynx. Furthermore, several ASC progeny markers were downregulated, and regeneration was impaired. Here we found that SmedOB1 is required for telomeric DNA-protein complex formation and it associates with the telomere TTAGGG sequence in vitro. Moreover, DNA damage and apoptosis signals in planarian were significantly affected by SmedOB1 RNAi. We also confirmed these phenotypes in Dugesia japonica, another flatworm species. Our work identified a novel telomere-associated protein SmedOB1 in planarian, which is required for planarian homeostasis and regeneration. The phylogenetic and functional conservations of SmedOB1 provide one mechanism by which planarians maintain telomere and genome stability to ensure their immortality and shed light on the regeneration medicine of humans.
Highlights
Adult stem cells (ASCs) self-renew and give rise to multiple cell types during tissue homeostasis and regeneration[1,2]
We identified a novel telomere associated SmedOB1 protein that is required for freshwater planarian homeostasis and regeneration, indicating that this telomere-associated protein is crucial for planarians to maintain telomeres and genome stability to ensure their immortality
We used the sequence from the longest isoform of human protection of telomeres 1 (POT1) to search the Schmidtea mediterranea genome database and found that the 333-bp genome sequence V31.002347: 3945..3613 was a significant match
Summary
Adult stem cells (ASCs) self-renew and give rise to multiple cell types during tissue homeostasis and regeneration[1,2]. Human POT1 was originally cloned based on its sequence homology to TEBPαand is critical for ensuring proper telomere length control and stability[7,8]. Inhibiting SmedOB1 expression may disrupt stem cell self-renewal causing DNA damage and apoptosis. Loss of SmedOB1 significantly increased the DNA damage as well as apoptosis signals in planarian. We confirmed these phenotypes in another flatworm species, Dugesia japonica. We identified a novel telomere associated SmedOB1 protein that is required for freshwater planarian homeostasis and regeneration, indicating that this telomere-associated protein is crucial for planarians to maintain telomeres and genome stability to ensure their immortality
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