59 research outputs found

    RBM5 Is a Male Germ Cell Splicing Factor and Is Required for Spermatid Differentiation and Male Fertility

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    Alternative splicing of precursor messenger RNA (pre-mRNA) is common in mammalian cells and enables the production of multiple gene products from a single gene, thus increasing transcriptome and proteome diversity. Disturbance of splicing regulation is associated with many human diseases; however, key splicing factors that control tissue-specific alternative splicing remain largely undefined. In an unbiased genetic screen for essential male fertility genes in the mouse, we identified the RNA binding protein RBM5 (RNA binding motif 5) as an essential regulator of haploid male germ cell pre-mRNA splicing and fertility. Mice carrying a missense mutation (R263P) in the second RNA recognition motif (RRM) of RBM5 exhibited spermatid differentiation arrest, germ cell sloughing and apoptosis, which ultimately led to azoospermia (no sperm in the ejaculate) and male sterility. Molecular modelling suggested that the R263P mutation resulted in compromised mRNA binding. Within the adult mouse testis, RBM5 localises to somatic and germ cells including spermatogonia, spermatocytes and round spermatids. Through the use of RNA pull down coupled with microarrays, we identified 11 round spermatid-expressed mRNAs as putative RBM5 targets. Importantly, the R263P mutation affected pre-mRNA splicing and resulted in a shift in the isoform ratios, or the production of novel spliced transcripts, of most targets. Microarray analysis of isolated round spermatids suggests that altered splicing of RBM5 target pre-mRNAs affected expression of genes in several pathways, including those implicated in germ cell adhesion, spermatid head shaping, and acrosome and tail formation. In summary, our findings reveal a critical role for RBM5 as a pre-mRNA splicing regulator in round spermatids and male fertility. Our findings also suggest that the second RRM of RBM5 is pivotal for appropriate pre-mRNA splicing.This work was supported by grants from the National Health and Medical Research Council (NHMRC) to DJ (#606503); the Australian Research Council (ARC) to MKO and CJO; the New South Wales Cancer Council, Cancer Institute New South Wales, Banque Nationale de Paris-Paribas Australia and New Zealand, RT Hall Trust, and the National Breast Cancer Foundation to CJO. DJ was an NHMRC Peter Doherty Postdoctoral Fellow (#384297). MKO and CJO are NHMRC Senior Research Fellows (#545805, #481310). CCG is an NHMRC Australia Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Contexts, diversity, pathways : advances and next steps

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    This chapter - a commentary - has two aims. One is to indicate how the several chapters advance our analyses of contexts, diversity, and pathways. The other is to suggest some further steps. The material is in three sections, taking up , in turn, the three topics. They are linked topics, but I take them up separately, with comments on interweaving as we proceed. I also place contexts first. For me, the way we approach contexts sets the stage for how we think about diversity and pathways. In all sections, the material covered is necessarily selective, both because of space and because, for all that I have learned from other disciplines, psychology remains the field I know best and most wish to see change

    Research and action : challenges, moves forward and unfinished tasks

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    Parents' knowledge and expectations : using what we know

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    22 page(s

    Ethnicity : spotlight on person-context interactions

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    Adding culture to studies of development : toward changes in procedure and theory

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    This paper asks how an interest in culture and in development can be combined to the benefit of both and at the level of theory and procedures. Three steps are considered, noting for each some existing moves and some recommended extensions. The first step has to do with the sampling of people. Here the main existing move has been toward greater social diversity in sampling. The extensions have to do with giving closer attention to the bases for choice, the ‘subjects’ view of events, within-group diversity or consensus, and one’s own culture. The second step has to do with sampling tasks and situations. Here the existing moves have been toward the greater use of everyday tasks, life-course problems, and tasks that involve two or more people: all shifts based on changes in concepts of ability and its bases. The extensions have to do with considering larger groups (going beyond dyads), the impact of audiences, the expectations people hold about appropriate contributions to shared tasks, and the conceptual bases for choice. The third step consists of alertness to unexpected or missing pieces in data or theory. It is illustrated by progressions within research by Peggy Miller and by the author and her colleagues (e.g., progressions in the latter case from Piagetian tasks to parents’ concepts of development and household divisions of labour).9 page(s

    The Benefits of cross-cultural collaboration

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    Family socialization : new moves and next steps

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    The areas considered in this chapter have to do with the aims of family socialization, the nature of influence, linking multiple sources of influence, and the range of families and contexts used as a basis for accounts of socialization. In each area, moving beyond restrictive assumptions opens up new ways of thinking and new research questions
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