RBM20 Regulates Circular RNA Production From the Titin Gene

RNA-binding motif protein 20 (RBM20) is essential for normal splicing of many cardiac genes, and loss of RBM20 causes dilated cardiomyopathy. Given its role in splicing, we hypothesized an important role for RBM20 in forming circular RNAs (circRNAs), a novel class of noncoding RNA molecules. To establish the role of RBM20 in the formation of circRNAs in the heart. Here, we performed circRNA profiling on ribosomal depleted RNA from human hearts and identified the expression of thousands of circRNAs, with some of them regulated in disease. Interestingly, we identified 80 circRNAs to be expressed from the titin gene, a gene that is known to undergo highly complex alternative splicing. We show that some of these circRNAs are dynamically regulated in dilated cardiomyopathy but not in hypertrophic cardiomyopathy. We generated RBM20-null mice and show that they completely lack these titin circRNAs. In addition, in a cardiac sample from an RBM20 mutation carrier, titin circRNA production was severely altered. Interestingly, the loss of RBM20 caused only a specific subset of titin circRNAs to be lost. These circRNAs originated from the RBM20-regulated I-band region of the titin transcript. We show that RBM20 is crucial for the formation of a subset of circRNAs that originate from the I-band of the titin gene. We propose that RBM20, by excluding specific exons from the pre-mRNA, provides the substrate to form this class of RBM20-dependent circRNA

Builders, bodies and bifurcations: How London construction workers 'learn to labour'

This article examines how the ideas about working-class culture presented in Paul Willis?s classic monograph (1977) Learning to Labour apply or do not apply to the data generated by an ethnographic analysis of a London construction site that I conducted in 2003/4. While Learning to Labour had significant relevance to understanding the class-bound masculine cultures of the construction workers, because building work has a pre-industrial history and a post-industrial contemporary, the claim that working-class masculinity is driven predominately by the features of industrial work life is found wanting. Rather than being bound exclusively to industrial work, the exigencies of working-class-bound masculinity could be found in the builders? problematic and attenuated relationships with the modern state and its legal and moral injunctions. Such relationships to the modern state illuminate why fundamental features of working-class masculine culture are reproduced in a post-industrial global London by both migrant and more indigenous workers, and thus also illustrate part of the reason why class and ethnic inequality persist in the contemporary UK