Deregulated RNA quality control leads to impaired regeneration and aging-like phenotypes in a non-senescent animal

Non-coding RNA is recognized as an important factor in many cellular functions, but how far the effects of deregulated non-coding RNA can reach is not fully understood. Here, we show that the global phenotypes of poor wound closure, reduced regeneration, and deregulated proteostasis, as commonly associated with aging, can be caused by deregulation of non-coding RNA.Planarians have proficient regenerative abilities that do not decline with age. The conserved RNA regulatory PIWI protein SMEDWI-1 is retained in the adult pluripotent stem cells of planarians throughout their life. We previously found that loss of SMEDWI-1 results in accumulation of non-coding and aberrant RNAs in stem cells, and reduction of stem cell resilience. We now find that animals lacking SMEDWI-1 with time also develop deficiencies in regeneration that involve defects in wound closure. We find that such animals have altered organization of extracellular collagen in the basement membrane and at the wound site, as well as deregulation of secreted structures in the epidermis that support epidermal barrier function. Further, they show signs of intracellular protein aggregation. Our data indicate that these defects result from the misregulation of the Signal Recognition Particle (SRP), which is responsible for co-translational protein secretion, and consists of protein and non-coding RNA components. Misregulation of non-coding RNA, such as in smedwi-1(RNAi) animals, thus can lead to imbalances in essential cellular machinery including the SRP, resulting in far-reaching organismal defects.