Enhanced RNA quality control maintains long-term regenerative ability in planarians.

Abstract

Planarians have proficient regenerative abilities that persist undiminished throughout adulthood, mediated by their stem cells (neoblasts). It is unclear how planarians accomplish this, as most animals show age-related declines in health and regeneration. Neoblasts express the conserved RNA regulatory PIWI protein SMEDWI-1, homologs of which are found in germ cells and long-lived cells in other systems. We previously found that loss of SMEDWI-1 from the neoblasts results in accumulation of non-coding and aberrant RNAs. Here, we report that over time SMEDWI-1-depleted animals develop defects in wound repair and regeneration, alterations in secreted proteins, and increased intracellular protein aggregation. Our data indicate that these defects result from misassembly of the Signal Recognition Particle (SRP), a ribonucleoprotein (RNP) responsible for co-translational protein secretion, that contains a non-coding RNA as a scaffold. In the absence of tight regulation of non-coding RNA as provided by SMEDWI-1, gradual accumulation of RNAs leads to imbalances in essential cellular machinery such as the SRP, resulting in compromised proteostasis and progressive loss of organismal vigor.