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

H19 long noncoding RNA controls the mRNA decay promoting function of KSRP

Long noncoding RNAs (lncRNAs) interact with protein factors to regulate different layers of gene expression transcriptionally or posttranscriptionally. Here we report on the functional consequences of the unanticipated interaction of the RNA binding protein K homology-type splicing regulatory protein (KSRP) with the H19 lncRNA (H19). KSRP directly binds to H19 in the cytoplasm of undifferentiated multipotent mesenchymal C2C12 cells, and this interaction favors KSRP-mediated destabilization of labile transcripts such as myogenin. AKT activation induces KSRP dismissal from H19 and, as a consequence, myogenin mRNA is stabilized while KSRP is repurposed to promote maturation of myogenic microRNAs, thus favoring myogenic differentiation. Our data indicate that H19 operates as a molecular scaffold that facilitates effective association of KSRP with myogenin and other labile transcripts, and we propose that H19 works with KSRP to optimize an AKT-regulated posttranscriptional switch that controls myogenic differentiation

KH domains with impaired nucleic acid binding as a tool for functional analysis

In eukaryotes, RNA-binding proteins that contain multiple K homology (KH) domains play a key role in coordinating the different steps of RNA synthesis, metabolism and localization. Understanding how the different KH modules participate in the recognition of the RNA targets is necessary to dissect the way these proteins operate. We have designed a KH mutant with impaired RNA-binding capability for general use in exploring the role of individual KH domains in the combinatorial functional recognition of RNA targets. A double mutation in the hallmark GxxG loop (GxxG-to-GDDG) impairs nucleic acid binding without compromising the stability of the domain. We analysed the impact of the GDDG mutations in individual KH domains on the functional properties of KSRP as a prototype of multiple KH domain-containing proteins. We show how the GDDG mutant can be used to directly link biophysical information on the sequence specificity of the different KH domains of KSRP and their role in mRNA recognition and decay. This work defines a general molecular biology tool for the investigation of the function of individual KH domains in nucleic acid binding proteins

Economic crisis and the construction of a neo-liberal regulatory regime in Korea

A consistent theme of the literature on the ontology of the 1997 South Korean crisis is the key role played by regulatory failures and the growing weakness of the state. This paper seeks to briefly highlight both the insights and the limitations of this approach to understanding the crisis. Having done so, we shall set out the argument that the crisis created an opportunity for reformist Korean élites to advance their longstanding, but previously frustrated, project to create a comprehensive unambiguously neo-liberal regulatory regime. This paper will also seek to highlight the implications of our reading of the development of the Korean political economy for broader debates on economic liberalisation, crisis and the future of the developmental state

Una pellicola di carta: analisi linguistica della trasposizione cinematografica de «L’isola di Arturo»

Oggetto di questo articolo è l’analisi linguistica della trasposizione cinematografica de L’Isola di Arturo,  pellicola tratta dall’omonimo romanzo morantiano e proiettata nelle sale italiane il 21 Dicembre del 1962 sotto la regia di Damiano Damiani. Lo studio si propone di mettere in luce, attraverso un caso particolare, l’inscindibilità del binomio cinema-parola, cercando di rendere esplicite le tecniche di elaborazione della lingua riprodotta nei dialoghi filmici e di delineare il rapporto multiforme che lega ogni adattamento alla sua fonte letteraria nella consapevolezza che ogni traduzione sia un’operazione di ricreazione artistica volta a rinnovare l’opera di riferimento. This paper revolves around the linguistical analysis of the film adaptation of Arturo’s Island, based on the homonymous novel by Elsa Morante and released in Italian theatres on December 21st, 1962, directed by Damiano Damiani. This paper’s goal is to highlight, using a specific case, the indissolubility of the binomial film-word, to make explicit the elaboration techniques of language in movie dialogue and to outline the multiform relationship that binds all cinematic adaptations to its literary inspiration, in the conscious knowledge that each translation is an operation of artistic recreation, meant to renovate the work it is based upon

Psychological attributes of individual investors in finanical markets

The aim of this thesis is to understand which psychological attributes are important in explaining investors observed behavior within the financial markets and the economy. The dataset used for most part of the thesis consists of UK based individual investors. This research involves analysis of investors selective attention to information conditional on the past stock market returns and investors’ personality trait of neuroticism. The study also includes cross-sectional analysis of investors’ portfolio performance, risk preferences and trading behavior and how these relate to various self-reported psychological attributes. Lastly this study explores the impact of arousal and psychological attributes on investors’ trading behavior within an experimental framework. Standard models of economics assume that individuals are omniscient rational utility maximizers with stable risk preferences and such models leave no room for individual differences and emotions. The results of the current research provide evidence that psychological attributes play an important role in financial decision making and account for significant variation in investors’ information acquisition decisions, frequency of trades, risk preferences and portfolio performance. The objective of this thesis is to contribute to the growing field of behavioral finance by providing a finer picture of investors’ behavior and by suggesting alternative explanations that better reflect the behavior of the agents that populate the real worl

A cytoplasmic variant of the KH-type splicing regulatory protein serves as a decay-promoting factor for phosphoglycerate kinase 2 mRNA in murine male germ cells

Phosphoglycerate kinase 2 (PGK2) is a germ cell-specific protein whose mRNA is translationally regulated in the mammalian testis. Using RNA affinity chromatography with the 3′-untranslated region (UTR) of Pgk2 mRNA and adult testis extracts, several associated proteins including a novel isoform of the AU-rich element RNA-binding protein and KH-type splicing regulatory protein (KSRP) were identified. KSRP, a protein of ∼75 kDa, is widely expressed in somatic and germ cells where it is primarily nuclear. In addition to the ∼75-kDa KSRP, a ∼52-kD KSRP, t-KSRP, is present in the cytoplasm of a subpopulation of germ cells. t-KSRP binds directly to a 93-nt sequence (designated the F1 region) of the 3′-UTR of the Pgk2 mRNA and destabilizes Pgk2 mRNA constructs in testis extracts and in transfected cells. We conclude that this testicular variant of the multifunctional nucleic acid–binding protein, KSRP, serves as a decay-promoting factor for Pgk2 mRNA in male germ cells

Chest wall resection and reconstruction by composite prosthesis for locally recurrent breast carcinoma

status: publishe