Graphical Abstract Highlights d Most nuclear exosome targeted loci produce NEXT-and PAXT-sensitive RNA isoforms d NEXT targets non-polyadenylated RNA 3 0 ends distributed over kilobase-wide regions d PAXT targets polyadenylated RNA 3 0 ends generated by CPSF at canonical poly(A) sites d NEXT targets are polyadenylated upon NEXT depletion, allowing exosomal decay via PAXT

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Organs are anatomically compartmentalised to cater for specialised functions. In the small intestine (SI), regionalisation enables sequential processing of food and nutrient absorption. While several studies indicate the critical importance of non-epithelial cells during development and homeostasis, the extent to which these cells contribute to regionalisation during morphogenesis remains unexplored. Here, we identify a mesenchymal-epithelial crosstalk that shapes the developing SI during late morphogenesis. We find that subepithelial mesenchymal cells are characterised by gradients of factors supporting Wnt signalling and stimulate epithelial growth in vitro. Such a gradient impacts epithelial gene expression and regional villus formation along the anterior-posterior axis of the SI. Notably, we further provide evidence that Wnt signalling directly regulates epithelial expression of Sonic Hedgehog (SHH), which, in turn, acts on mesenchymal cells to drive villi formation. Taken together our results uncover a mechanistic link between Wnt and Hedgehog signalling across different cellular compartments that is central for anterior-posterior regionalisation and correct formation of the SI.

Highlights d Depletion of ZFC3H1 in mouse ESCs results in differentiation defects d PRC2 target genes are deregulated in Zfc3h1 À/À cells d Chromatin binding of PRC2 and H3K27me3 is reduced in Zfc3h1 À/À cells d Increased binding of RNA impairs PRC2 complex stability

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article.