Schmidt, DavidReuter, HannaHüttner, KatjaRuhe, LarissaRabert, FranziskaSeebeck, FlorianIrimia Martínez, ManuelSolana, JordiBartscherer, Kerstin2019-12-042019-12-042018Schmidt D, Reuter H, Hüttner K, Ruhe L, Rabert F, Seebeck F et al. The Integrator complex regulates differential snRNA processing and fate of adult stem cells in the highly regenerative planarian Schmidtea mediterranea. PLoS Genet. 2018;14(12):e1007828. DOI: 10.1371/journal.pgen.10078281553-7390http://hdl.handle.net/10230/43081In multicellular organisms, cell type diversity and fate depend on specific sets of transcript isoforms generated by post-transcriptional RNA processing. Here, we used Schmidtea mediterranea, a flatworm with extraordinary regenerative abilities and a large pool of adult stem cells, as an in vivo model to study the role of Uridyl-rich small nuclear RNAs (UsnRNAs), which participate in multiple RNA processing reactions including splicing, in stem cell regulation. We characterized the planarian UsnRNA repertoire, identified stem cell-enriched variants and obtained strong evidence for an increased rate of UsnRNA 3’-processing in stem cells compared to their differentiated counterparts. Consistently, components of the Integrator complex showed stem cell-enriched expression and their depletion by RNAi disrupted UsnRNA processing resulting in global changes of splicing patterns and reduced processing of histone mRNAs. Interestingly, loss of Integrator complex function disrupted both stem cell maintenance and regeneration of tissues. Our data show that the function of the Integrator complex in UsnRNA 3’-processing is conserved in planarians and essential for maintaining their stem cell pool. We propose that cell type-specific modulation of UsnRNA composition and maturation contributes to in vivo cell fate choices, such as stem cell self-renewal in planarians.application/pdfeng© 2018 Schmidt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.pgen.1007828RNA interferenceSmall nuclear RNAIntegratorsSequence motif analysisPlanariansCell differentiationRNA sequencingRNA splicinginfo:eu-repo/semantics/openAccess