Planarians recruit piRNAs for mRNA turnover in adult stem cells

PIWI proteins utilize small RNAs called piRNAs to silence transposable elements, thereby protecting germline integrity. In planarian flatworms, PIWI proteins are essential for regeneration, which requires adult stem cells termed neoblasts. Here, we characterize planarian piRNAs and examine the roles of PIWI proteins in neoblast biology. We find that the planarian PIWI proteins SMEDWI-2 and SMEDWI-3 cooperate to degrade active transposons via the ping-pong cycle. Unexpectedly, we discover that SMEDWI-3 plays an additional role in planarian mRNA surveillance. While SMEDWI-3 degrades numerous neoblast mRNAs in a homotypic ping-pong cycle, it is also guided to another subset of neoblast mRNAs by antisense piRNAs and binds these without degrading them. Mechanistically, the distinct activities of SMEDWI-3 are primarily dictated by the degree of complementarity between target mRNAs and antisense piRNAs. Planarian PIWI proteins thus act as both nucleases and RNA-binding proteins, enabling planarians to repurpose piRNAs for critical roles in neoblast mRNA turnover.

PIWI蛋白（PIWI proteins）通过一类名为piRNA（piRNAs）的小RNA沉默转座因子（transposable elements），从而维持生殖系完整性。在涡虫（planarian flatworms）中，PIWI蛋白对于再生过程至关重要，而该过程依赖于一类被称为成体干细胞（neoblasts）的成体干细胞群。本研究对涡虫piRNA进行了系统表征，并探究了PIWI蛋白在成体干细胞生物学中的功能。研究发现，涡虫PIWI蛋白SMEDWI-2与SMEDWI-3可通过乒乓循环（ping-pong cycle）协同降解活跃的转座因子。出乎意料的是，本研究还发现SMEDWI-3在涡虫mRNA监控中具备额外功能：尽管SMEDWI-3可通过同源乒乓循环降解大量成体干细胞mRNA，但它也可被反义piRNA（antisense piRNAs）引导至另一组成体干细胞mRNA，并与之结合而不发生降解。从机制层面来看，SMEDWI-3的双重活性主要由靶标mRNA与反义piRNA之间的互补程度决定。综上，涡虫PIWI蛋白兼具核酸酶与RNA结合蛋白的双重功能，使得涡虫能够重新利用piRNA，使其在成体干细胞mRNA代谢周转中发挥关键作用。