Unpacking the Area-Based Approach for Sustainable Urban Development in Europe: Policies and Challenges for Migrants Inclusion in the Metropolitan Area of Venice

The paper aims at disentangling the area-based approach as promoted by the EU to bring about integrated sustainable development in European urban areas. In particular, the paper looks at how this approach has evolved over time and to what extent it has been used to foster the inclusion of migrants through a territorialised or spatial perspective. This paper draws on the experience of the metropolitan area of Venice and the two Sustainable Urban Development strategies implemented there within the framework of the EU cohesion policy 2014-2020. It presents general reflections that shed light on the meaning and scope of the area-based approach in contemporary European cities, as well as the challenges that policy-makers encounter when putting it into practice. In particular, the paper acknowledges the attention to broader scales ‘beyond the neighbourhood’ that frames current EU policies for urban areas, but considers it insufficient. Instead, attention should also be given to a more granular scale that in certain cases, may involve single streets, part of streets, or even single buildings.The paper is published by the European Journal of Spatial Development (EJSD). The previous version of the journal was host by Nordregio

Unpacking the Area-Based Approach for Sustainable Urban Development in Europe: Policies and Challenges for Migrants Inclusion in the Metropolitan Area of Venice

The paper aims at disentangling the area-based approach as promoted by the EU to bring about integrated sustainable development in European urban areas. In particular, the paper looks at how this approach has evolved over time and to what extent it has been used to foster the inclusion of migrants through a territorialised or spatial perspective. This paper draws on the experience of the metropolitan area of Venice and the two Sustainable Urban Development strategies implemented there within the framework of the EU cohesion policy 2014-2020. It presents general reflections that shed light on the meaning and scope of the area-based approach in contemporary European cities, as well as the challenges that policy-makers encounter when putting it into practice. In particular, the paper acknowledges the attention to broader scales ‘beyond the neighbourhood’ that frames current EU policies for urban areas, but considers it insufficient. Instead, attention should also be given to a more granular scale that in certain cases, may involve single streets, part of streets, or even single buildings

Unpacking the Area-Based Approach for Sustainable Urban Development in Europe: Policies and Challenges for Migrants Inclusion in the Metropolitan Area of Venice

The paper aims at disentangling the area-based approach as promoted by the EU to bring about integrated sustainable development in European urban areas. In particular, the paper looks at how this approach has evolved over time and to what extent it has been used to foster the inclusion of migrants through a territorialised or spatial perspective. This paper draws on the experience of the metropolitan area of Venice and the two Sustainable Urban Development strategies implemented there within the framework of the EU cohesion policy 2014-2020. It presents general reflections that shed light on the meaning and scope of the area-based approach in contemporary European cities, as well as the challenges that policy-makers encounter when putting it into practice. In particular, the paper acknowledges the attention to broader scales ‘beyond the neighbourhood’ that frames current EU policies for urban areas, but considers it insufficient. Instead, attention should also be given to a more granular scale that in certain cases, may involve single streets, part of streets, or even single buildings

Comprehensive multi-omics analysis uncovers a group of TGF-β-regulated genes among lncRNA EPR direct transcriptional targets

Abstract Long non-coding RNAs (lncRNAs) can affect multiple layers of gene expression to control crucial cellular functions. We have previously demonstrated that the lncRNA EPR, by controlling gene expression at different levels, affects cell proliferation and migration in cultured mammary gland cells and impairs breast tumor formation in an orthotopic transplant model in mice. Here, we used ChIRP-Seq to identify EPR binding sites on chromatin of NMuMG mammary gland cells overexpressing EPR and identified its trans binding sites in the genome. Then, with the purpose of relating EPR/chromatin interactions to the reshaping of the epitranscriptome landscape, we profiled histone activation marks at promoter/enhancer regions by ChIP-Seq. Finally, we integrated data derived from ChIRP-Seq, ChIP-Seq as well as RNA-Seq in a comprehensive analysis and we selected a group of bona fide direct transcriptional targets of EPR. Among them, we identified a subset of EPR targets whose expression is controlled by TGF-β with one of them—Arrdc3—being able to modulate Epithelial to Mesenchymal Transition. This experimental framework allowed us to correlate lncRNA/chromatin interactions with the real outcome of gene expression and to start defining the gene network regulated by EPR as a component of the TGF-β pathway

Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding

The AU-rich element (ARE)-mediated mRNA-degradation activity of the RNA binding K-homology splicing regulator protein (KSRP) is regulated by phosphorylation of a serine within its N-terminal KH domain (KH1). In the cell, phosphorylation promotes the interaction of KSRP and 14-3-3ζ protein and impairs the ability of KSRP to promote the degradation of its RNA targets. Here we examine the molecular details of this mechanism. We report that phosphorylation leads to the unfolding of the structurally atypical and unstable KH1, creating a site for 14-3-3ζ binding. Using this site, 14-3-3ζ discriminates between phosphorylated and unphosphorylated KH1, driving the nuclear localization of KSRP. 14-3-3ζ –KH1 interaction regulates the mRNA-decay activity of KSRP by sequestering the protein in a separate functional pool. This study demonstrates how an mRNA-degradation pathway is connected to extracellular signaling networks through the reversible unfolding of a protein domain.European Molecular Biology Organization 240-2005Italian CIPE-200

A place-based approach to migrant integration

This Science for Policy report focuses on urban and territorial strategies promoted by the EU Cohesion Policy during the 2014-2020 programming period, namely Sustainable Urban Development (SUD), Integrated Territorial Investment (ITI) and Community-led Local Development (CLLD), and explores whether and how they may contribute to the integration and inclusion of international migrants in the local context. The study illustrates the findings of the Joint Research Centre (JRC) Exploratory Research Activity (ERA) International migrants in Functional Urban Areas. How strategies of sustainable urban development can foster the integration of migrants?, which integrates two analytical approaches, with in-depth case studies based on local data and performed by local academics complementing the analysis carried out at EU-level

KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells

<p>Abstract</p> <p>Background</p> <p>Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally through the binding of the <it>trans-</it>acting proteins AU rich binding factor 1 (AUF1), Upstream of N-<it>ras </it>(Unr) and KH-type splicing regulatory protein (KSRP) to an AU rich element (ARE) in PTH mRNA 3'-UTR. AUF1 and Unr stabilize PTH mRNA while KSRP, recruiting the exoribonucleolytic complex exosome, promotes PTH mRNA decay.</p> <p>Results</p> <p>PTH mRNA is cleaved by the endoribonuclease polysomal ribonuclease 1 (PMR1) in an ARE-dependent manner. Moreover, PMR1 co-immunoprecipitates with PTH mRNA, the exosome and KSRP. Knock-down of either exosome components or KSRP by siRNAs prevents PMR1-mediated cleavage of PTH mRNA.</p> <p>Conclusion</p> <p>PTH mRNA is a target for the endonuclease PMR1. The PMR1 mediated decrease in PTH mRNA levels involves the PTH mRNA 3'-UTR ARE, KSRP and the exosome. This represents an unanticipated mechanism by which the decay of an ARE-containing mRNA is facilitated by KSRP and is dependent on both the exosome and an endoribonuclease.</p

Identification of a set of KSRP target transcripts upregulated by PI3K-AKT signaling

BACKGROUND: KSRP is a AU-rich element (ARE) binding protein that causes decay of select sets of transcripts in different cell types. We have recently described that phosphatidylinositol 3-kinase/AKT (PI3K-AKT) activation induces stabilization and accumulation of the labile β-catenin mRNA through an impairment of KSRP function. RESULTS: Aim of this study was to identify additional KSRP targets whose stability and steady-state levels are enhanced by PI3K-AKT activation. First, through microarray analyses of the AU-rich transcriptome in pituitary αT3-1 cells, we identified 34 ARE-containing transcripts upregulated in cells expressing a constitutively active form of AKT1. In parallel, by an affinity chromatography-based technique followed by microarray analyses, 12 mRNAs target of KSRP, additional to β-catenin, were identified. Among them, seven mRNAs were upregulated in cells expressing activated AKT1. Both steady-state levels and stability of these new KSRP targets were consistently increased by either KSRP knock-down or PI3K-AKT activation. CONCLUSION: Our study identified a set of transcripts that are targets of KSRP and whose expression is increased by PI3K-AKT activation. These mRNAs encode RNA binding proteins, signaling molecules and a replication-independent histone. The increased expression of these gene products upon PI3K-AKT activation could play a role in the cellular events initiated by this signaling pathway

The RNA-Binding Protein KSRP Promotes Decay of β-Catenin mRNA and Is Inactivated by PI3K-AKT Signaling

β-catenin plays an essential role in several biological events including cell fate determination, cell proliferation, and transformation. Here we report that β-catenin is encoded by a labile transcript whose half-life is prolonged by Wnt and phosphatidylinositol 3-kinase–AKT signaling. AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRP's ability to promote rapid mRNA decay. Our results uncover an unanticipated level of control of β-catenin expression pointing to KSRP as a required factor to ensure rapid degradation of β-catenin in unstimulated cells. We propose KSRP phosphorylation as a link between phosphatidylinositol 3-kinase–AKT signaling and β-catenin accumulation