Quaking Regulates Hnrnpa1 Expression through Its 3′ UTR in Oligodendrocyte Precursor Cells

In mice, Quaking (Qk) is required for myelin formation; in humans, it has been associated with psychiatric disease. QK regulates the stability, subcellular localization, and alternative splicing of several myelin-related transcripts, yet little is known about how QK governs these activities. Here, we show that QK enhances Hnrnpa1 mRNA stability by binding a conserved 3′ UTR sequence with high affinity and specificity. A single nucleotide mutation in the binding site eliminates QK-dependent regulation, as does reduction of QK by RNAi. Analysis of exon expression across the transcriptome reveals that QK and hnRNP A1 regulate an overlapping subset of transcripts. Thus, a simple interpretation is that QK regulates a large set of oligodendrocyte precursor genes indirectly by increasing the intracellular concentration of hnRNP A1. Together, the data show that hnRNP A1 is an important QK target that contributes to its control of myelin gene expression

The consciousness of history in the novels of Nadine Gordimer

SIGLELD:D49588/84 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Bram Fischer and the Question of Identity

In January 1965, Bram Fischer disappeared from his trial in Johannesburg on charges under the Suppression of Communism Act, beginning a period for him of ten months underground and in disguise. This essay takes that starting point to consider key questions of identity for Fischer, for South Africa, and for a wider world. Fischer was groomed for leadership within an eminent Afrikaner nationalist family, yet came to identify himself with the majority of South Africa’s people, helping to forge a new version of what South African identity could mean. The essay explores key foundations of such a development, based on the concepts of displacement and a ‘grammar of identity’ which works through a principle of combination, both within the self and beyond

Defect-mediated creep of structured materials

Low-stress creep measurements on a nematic liquid crystal polymer indicate that it is a viscoelastic solid, with a modulus of $100 {dynes/cm^{2}}$ and a yield stress of $50 {dynes/cm^{2}}$. Both smectics and nematics are viscoelastic solids at very low stress levels, with a modulus that is related to their defect texture. At stress levels somewhat above the yield stress, there is a yielding regime where the deformation rate and defect spacing are power laws in the applied stress. We understand these power laws using the ideas developed long ago by Orowan for the motion of line defects in crystalline solids. The exponents of these power laws are different for nematics and smectics, but the nematic universality class also appears to apply to superplastic metals and ceramics

A conserved three-nucleotide core motif defines Musashi RNA binding specificity

Musashi (MSI) family proteins control cell proliferation and differentiation in many biological systems. They are overexpressed in tumors of several origins, and their expression level correlates with poor prognosis. MSI proteins control gene expression by binding RNA and regulating its translation. They contain two RNA recognition motif (RRM) domains, which recognize a defined sequence element. The relative contribution of each nucleotide to the binding affinity and specificity is unknown. We analyzed the binding specificity of three MSI family RRM domains using a quantitative fluorescence anisotropy assay. We found that the core element driving recognition is the sequence UAG. Nucleotides outside of this motif have a limited contribution to binding free energy. For mouse MSI1, recognition is determined by the first of the two RRM domains. The second RRM adds affinity but does not contribute to binding specificity. In contrast, the recognition element for Drosophila MSI is more extensive than the mouse homolog, suggesting functional divergence. The short nature of the binding determinant suggests that protein-RNA affinity alone is insufficient to drive target selection by MSI family proteins