Europe 2020 and the European Semester signal a major change of direction in EU social policy with new governance arrangements, policy orientations and politics. This paper analyses 290 Country ...Specific Recommendations and 29 interviews to answer two questions: 1) What type of social policy is being advanced by the EU at present? 2) How are EU social actors able to advance EU social policy under current conditions? It argues that the degree of progress in EU social policy in the European Semester (2011–15) has been conditional and contingent. EU social policy is more oriented to supporting market development than it is to correcting for market failures. We explain these developments by a combination of factors including the strong agency exerted by some social actors in a context of constraint, the moderation of expectations and the adoption of strategic practices by key actors, and political divisions among the Member States.
This article explains the relaunch of the European Union's (EU) economic reform agenda in 2010. After repeated delays during 2009, the European Commission scaled back its initial plan for a revived ...social dimension and instead proposed a strengthened governance architecture of economic surveillance. Using the multiple streams framework we argue that the new Europe 2020 strategy which emerged is a product of two overlapping policy windows which opened suddenly in the problem stream (the Greek sovereign debt crisis) and politics stream (shifting institutional dynamics). This created a window of opportunity for skilful policy entrepreneurs to 'couple' the three streams by reframing the existing Lisbon Strategy as the EU's exit strategy from the crisis. The article contributes to understanding policy change under conditions of ambiguity by demonstrating the causal significance of key temporal and ideational dynamics: the timing of policy windows; access to information signals; and the role of policy entrepreneurs.
Mutations affecting the SECISBP2 protein necessary for selenocysteine incorporation are linked to human disease, but with a wide range of clinical outcomes. To gain insight into this diversity, Zhao ...et al. dissect the phenotypic and molecular consequences of two specific mutations in the Secisbp2 gene that partially disrupt selenoprotein synthesis. They observe surprising tissue-dependent effects, emphasizing the complexities of translational science.
This article assesses the political and power dynamics of the Ordinarily Legislative Procedure (OLP) in social Europe and the likely impact of the UK’s departure in the field for future integration. ...It provides a detailed analysis of the OLP in social Europe during two recent periods of integration in the field—the first Barroso Commission (2004–2009) and the Juncker Commission (2014–2019). It finds the dynamics of the OLP have shifted from intergovernmental deadlock during the Barroso Commission to the characteristics of a new intergovernmental core state power during the Juncker Commission, even though the policy area is not a core state power per se. Despite the use of qualified majority voting policy agreements can only be achieved when there is near unanimity support in the Council, the Commission remains a neutral broker, and the Parliament shifts its position to that of the Council. As a result, continued opposition to integration in social Europe by Northern and Eastern Members means the removal of UK political agency will have only a marginal impact on the slow and piecemeal approach to integration in the field.
Selenoproteins contain the 21st amino acid, selenocysteine (Sec), which is incorporated at select UGA codons when a specialized hairpin sequence, the Sec insertion sequence (SECIS) element, is ...present in the 3' UTR. Aside from the SECIS, selenoprotein mRNA 3' UTRs are not conserved between different selenoproteins within a species. In contrast, the 3'-UTR of a given selenoprotein is often conserved across species, which supports the hypothesis that cis-acting elements in the 3'-UTR other than the SECIS exert post-transcriptional control on selenoprotein expression. In order to determine the function of one such SECIS context, we chose to focus on the plasma selenoprotein, SELENOP, which is required to maintain selenium homeostasis as a selenium transport protein that contains 10 Sec residues. It is unique in that its mRNA contains two SECIS elements in the context of a highly conserved 843-nucleotide 3' UTR. Here we have used RNA affinity chromatography and identified PTBP1 as the major RNA binding protein that specifically interacts with the sequence between the two SECIS elements. We then used CRISPR/Cas9 genome editing to delete two regions surrounding the first SECIS element. We found that these sequences are involved in regulating SELENOP mRNA and protein levels, which are inversely altered as a function of selenium concentrations.
Selenocysteine (Sec) is a critical residue in at least 25 human proteins that are essential for antioxidant defense and redox signaling in cells. Sec is inserted into proteins cotranslationally by ...the recoding of an in-frame UGA termination codon to a Sec codon. In eukaryotes, this recoding event requires several specialized factors, including a dedicated, Sec-specific elongation factor called eEFSec, which binds Sec-tRNASec with high specificity and delivers it to the ribosome for selenoprotein production. Unlike most translation factors, including the canonical elongation factor eEF1A, eEFSec readily localizes to the nucleus of mammalian cells and shuttles between the cytoplasmic and nuclear compartments. The functional significance of eEFSec's nuclear localization has remained unclear. In this study, we have examined the subcellular localization of eEFSec in the context of altered Sec incorporation to demonstrate that reduced selenoprotein production does not correlate with changes in the nuclear localization of eEFSec. In addition, we identify several novel sequences of the protein that are essential for localization as well as Sec insertion activity, and show that eEFSec utilizes CRM1-mediated nuclear export pathway. Our findings argue for two distinct pools of eEFSec in the cell, where the cytoplasmic pool participates in Sec incorporation and the nuclear pool may be involved in an as yet unknown function.
Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated translation factors. Among the mammalian ...selenoproteins, Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.
In this review we elaborate on new data and current models that provide insight into how SELENOP is made.
SELENOP synthesis requires a specific set of factors and conditions.
As the key protein required for proper selenium distribution, SELENOP stands out as a lynchpin selenoprotein that is essential for male fertility, proper neurologic function and selenium metabolism.
•Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec).•Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.•SELENOP synthesis requires a unique set of factors and RNA structures.•SELENOP is essential for male fertility, proper neurologic function and selenium metabolism.
The amino acid selenocysteine (Sec) is encoded by UGA codons. Recoding of UGA from stop to Sec requires a Sec insertion sequence (SECIS) element in the 3' UTR of selenoprotein mRNAs. SECIS binding ...protein 2 (SBP2) binds the SECIS element and is essential for Sec incorporation into the nascent peptide. SBP2-like (SBP2L) is a paralogue of SBP2 in vertebrates and is the only SECIS binding protein in some invertebrates where it likely directs Sec incorporation. However, vertebrate SBP2L does not promote Sec incorporation in in vitro assays. Here we present a comparative analysis of SBP2 and SBP2L SECIS binding properties and demonstrate that its inability to promote Sec incorporation is not due to lower SECIS affinity but likely due to lack of a SECIS dependent domain association that is found in SBP2. Interestingly, however, we find that an invertebrate version of SBP2L is fully competent for Sec incorporation in vitro. Additionally, we present the first evidence that SBP2L interacts with selenoprotein mRNAs in mammalian cells, thereby implying a role in selenoprotein expression.
Decoding of genetic information into polypeptides occurs during translation, generally following the codon assignment rules of the organism's genetic code. However, recoding signals in certain mRNAs ...can overwrite the normal rules of translation. An exquisite example of this occurs during translation of selenoprotein mRNAs, wherein UGA codons are reassigned to encode for the 21st proteogenic amino acid, selenocysteine. In this review, we will examine what is known about the mechanisms of UGA recoding and discuss the fate of ribosomes that fail to incorporate selenocysteine.
Integration within the European social dimension, understood as the EU’s competence in the field of employment and social policy, has been fraught with obstacles. Divisions between the EU’s Member ...States have limited integration and resulted in a complex and piecemeal system of governance that is low down on the EU’s list of priorities. The UK is often regarded as a major obstacle limiting the scope of integration in the field and this is not without good reason. Historically, the UK has formed coalitions to block policy negotiations within the European Council and has pushed for minimal neoliberal obligations in the field. The UK’s departure from the EU could result in a step-change for the European social dimension. However, as this article will argue, the UK’s departure from the EU will do little to alter the current dominance of a neoliberal market-led ideology, as it currently transcends the political agency of the UK.
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