A falling of the veils: turning points and momentous turning points in leadership and the creation of CSR

This article uses the life stories approach to leadership and leadership development. Using exploratory, qualitative data from a Forbes Global 2000 and FTSE 100 company, we discuss the role of the turning point (TP) as an important antecedent of leadership in corporate social responsibility. We argue that TPs are causally efficacious, linking them to the development of life narratives concerned with an evolving sense of personal identity. Using both a multi-disciplinary perspective and a multi-level focus on CSR leadership, we identify four narrative cases. We propose that they helped to re-define individuals’ sense of self and in some extreme cases completely transformed their self-identity as leaders of CSR. Hence we also distinguish the momentous turning point (MTP) that created a seismic shift in personality, through re-evaluation of the individuals’ personal values. We argue that whilst TPs are developmental experiences that can produce responsible leadership, the MTP changes the individuals’ personal priorities in life to produce responsible leadership that perhaps did not exist previously. Thus we appropriate Maslow’s (1976, p. 77) metaphorical phrase ‘A falling of the veils’ from his discussion of peak and desolation experiences that produce personal growth. Using a multi-disciplinary literature from social theory (Archer, 2012) moral psychology (Narvaez, 2009) and social psychology (Schwartz, 2010), we present a theoretical model that illustrates the psychological process of the (M)TP, thus contributing to the growing literature on the microfoundations of CSR

Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges

Alternative splicing (AS) enables programmed diversity of gene expression across tissues and development. We show here that binding in distal intronic regions (>500 nucleotides (nt) from any exon) by Rbfox splicing factors important in development is extensive and is an active mode of splicing regulation. Similarly to exon-proximal sites, distal sites contain evolutionarily conserved GCATG sequences and are associated with AS activation and repression upon modulation of Rbfox abundance in human and mouse experimental systems. As a proof of principle, we validated the activity of two specific Rbfox enhancers in KIF21A and ENAH distal introns and showed that a conserved long-range RNA-RNA base-pairing interaction (an RNA bridge) is necessary for Rbfox-mediated exon inclusion in the ENAH gene. Thus we demonstrate a previously unknown RNA-mediated mechanism for AS control by distally bound RNA-binding proteins

The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain

The Rbfox family of RNA binding proteins regulates alternative splicing of many important neuronal transcripts but their role in neuronal physiology is not clear(1). We show here that central nervous system (CNS)-specific deletion of the Rbfox1 gene results in heightened susceptibility to spontaneous and kainic acid-induced seizures. Electrophysiological recording reveals a corresponding increase in neuronal excitability in the dentate gyrus of the knockout mice. Whole transcriptome analyses identify multiple splicing changes in the Rbfox1(−/−) brain with few changes in overall transcript abundance. These splicing changes alter proteins that mediate synaptic transmission and membrane excitation, some of which are implicated in human epilepsy. Thus, Rbfox1 directs a genetic program required in the prevention of neuronal hyperexcitation and seizures. The Rbfox1 knockout mice provide a new model to study the post-transcriptional regulation of synaptic function

RNA-binding protein CPEB1 remodels host and viral RNA landscapes

Host and virus interactions at the post-transcriptional level are critical for infection but remain poorly understood. Human cytomegalovirus (HCMV) is a prevalent herpesvirus family member that causes severe complications in immunocompromised patients and newborns. Here, we perform comprehensive transcriptome-wide analyses revealing that HCMV infection results in widespread alternative splicing (AS), shorter 3′-untranslated regions (3′UTRs) and polyA tail lengthening in host genes. The host RNA binding protein cytoplasmic polyadenylation element binding protein 1 (CPEB1) is highly induced upon infection and ectopic expression of CPEB1 in non-infected cells recapitulates infection-related post-transcriptional changes. CPEB1 is also required for polyA-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reverses infection-related cytopathology and post-transcriptional changes, and decreases productive HCMV titers. Host RNA processing is also altered in herpes simplex virus-2 (HSV-2) infected cells, indicating a common theme among herpesvirus infections. Our work is a starting point for therapeutic targeting of host RNA binding proteins in herpesvirus infections