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The Integrator complex regulates differential snRNA processing and fate of adult stem cells in the highly regenerative planarian Schmidtea mediterranea

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Item Type:Article
Title:The Integrator complex regulates differential snRNA processing and fate of adult stem cells in the highly regenerative planarian Schmidtea mediterranea
Creators Name:Schmidt, D. and Reuter, H. and Hüttner, K. and Ruhe, L. and Rabert, F. and Seebeck, F. and Irimia, M. and Solana, J. and Bartscherer, K.
Abstract:In 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.
Keywords:Adult Stem Cells, Base Sequence, Biological Models, Cell Differentiation, Cell Self Renewal, Helminth RNA, Nucleic Acid Conformation, Nucleic Acid Sequence Homology, RNA Interference, Post-Transcriptional RNA Processing, RNA Splicing, Small Nuclear RNA, Regeneration, Animals, Planarians
Source:PLoS Genetics
ISSN:1553-7404
Publisher:Public Library of Science (U.S.A.)
Volume:14
Number:12
Page Range:e1007828
Date:17 December 2018
Official Publication:https://doi.org/10.1371/journal.pgen.1007828
PubMed:View item in PubMed

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