The 90S pre-ribosome is an early biogenesis intermediate formed during co-transcriptional ribosome formation, composed of ∼70 assembly factors and several small nucleolar RNAs (snoRNAs) that associate with nascent pre-rRNA. We report the cryo-EM structure of the Chaetomium thermophilum 90S pre-ribosome, revealing how a network of biogenesis factors including 19 β-propellers and large α-solenoid proteins engulfs the pre-rRNA. Within the 90S pre-ribosome, we identify the UTP-A, UTP-B, Mpp10-Imp3-Imp4, Bms1-Rcl1, and U3 snoRNP modules, which are organized around 5'-ETS and partially folded 18S rRNA. The U3 snoRNP is strategically positioned at the center of the 90S particle to perform its multiple tasks during pre-rRNA folding and processing. The architecture of the elusive 90S pre-ribosome gives unprecedented structural insight into the early steps of pre-rRNA maturation. Nascent rRNA that is co-transcriptionally folded and given a particular shape by encapsulation within a dedicated mold-like structure is reminiscent of how polypeptides use chaperone chambers for their protein folding.
Ribosome biogenesis in eukaryotic cells is a highly dynamic and complex process innately linked to cell proliferation. The assembly of ribosomes is driven by a myriad of biogenesis factors that shape pre-ribosomal particles by processing and folding the ribosomal RNA and incorporating ribosomal proteins. Biochemical approaches allowed the isolation and characterization of pre-ribosomal particles from Saccharomyces cerevisiae, which lead to a spatiotemporal map of biogenesis intermediates along the path from the nucleolus to the cytoplasm. Here, we cloned almost the entire set (∼180) of ribosome biogenesis factors from the thermophilic fungus Chaetomium thermophilum in order to perform an in-depth analysis of their protein-protein interaction network as well as exploring the suitability of these thermostable proteins for structural studies. First, we performed a systematic screen, testing about 80 factors for crystallization and structure determination. Next, we performed a yeast 2-hybrid analysis and tested about 32,000 binary combinations, which identified more than 1000 protein-protein contacts between the thermophilic ribosome assembly factors. To exemplary verify several of these interactions, we performed biochemical reconstitution with the focus on the interaction network between 90S pre-ribosome factors forming the ctUTP-A and ctUTP-B modules, and the Brix-domain containing assembly factors of the pre-60S subunit. Our work provides a rich resource for biochemical reconstitution and structural analyses of the conserved ribosome assembly machinery from a eukaryotic thermophile.
How do states come to select norms? I contend that, given a number of conditions are present, states select norms in three ideal-typical stages: innovative argumentation, persuasive argumentation, and compromise+ This norm selection mechanism departs from the existing literature in two important ways+ First, my research elaborates on the literature on advocacy networks+ I explain why agents engage in an advocacy for a normative idea in the first place; I add the epistemic dimension of reasoning to argumentation theory; and I show in detail the pathways through which persuasive argumentation links an advocated idea and alreadyestablished sets of meaning+ Second, synthesizing rationalist and constructivist selection mechanisms, I contend that successful argumentation makes recalcitrant actors eager to reach a compromise with the advocates as long as this does not violate their most cherished beliefs+ The Republic of Ireland's eventual selection of the territorial status quo norm in the late 1990s lends empirical evidence to this norm selection mechanism+ This study addresses two pervasive aspects of the social world: argumentation and compromise+ Drawing on taken-for-granted ideas that enable us to make the world intelligible to ourselves, we make and exchange arguments to make up our minds about a particular issue and to persuade others to follow our reasoning+ Some arguments convince us+ We are persuaded by the line of reasoning that the argumentation contains+ Other arguments, by contrast, are unconvincing+ Of these unconvincing arguments, some violate our most deeply held beliefs+ They upset us and we reject them categorically+ Others, by contrast, do not violate our most profound beliefs+ We discard them with less vigor and are prepared to compromise on our stance+ I would like to thank of all, Emanuel Adler for very helpful comments on earlier versions of this article+ I am also greatly indebted to the anonymous reviewers and the editors of IO for their detailed and insightful comments+
International Relations takes it all too often for granted that different scholarly sub‐communities in the field are incommensurable and, therefore, that the erosion of the community of International Relations scholars is inevitable. I present a three‐fold argument against this inevitability: First, International Relations is much better understood as a field of overlapping horizons than a discipline of incommensurable paradigms. Second, the most consequential overlap is epistemological. This overlap is constituted by very specific rhetorical understandings of epistemology that come remarkably close to the Aristotelian Rhetoric and Philosophical Sophistic. International Relations is a rhetorical discipline. Third, dialogue is able to seize the opportunities for communication across different horizons within and beyond International Relations—making it a lively and open discipline instead of a constellation of hermetically sealed and self‐referential sub‐communities.
In Africa, the management of border disputes varies from sub-region to sub-region. Most puzzling is the difference between West Africa and the Horn of Africa. In the latter, border disputes are much more likely to escalate into war than in the former. Seeking to solve this puzzle, this study focuses on the territorial integrity norm. It departs from existing accounts of this norm in two ways: first, it does not choose the region but the sub-region as the level of analysis. Second, it does not isolate the territorial integrity norm from its social context but analyses the interplay of the norm with the social structure in which it is embedded. It concludes that the territorial integrity norm in West Africa is part of a social structure different from that in the Horn of Africa. It is this difference that explains the different patterns of conflict management in the two sub-regions.
Which uses of historical analogies help us compose an intelligible picture of international relations and which ones mislead us? This paper deals with this question on three levels. First, my epistemological argument makes a case for a rhetorical-pragmatist stance on historical analogies. I contend that critical discussion and adjudication make it possible to extract leads for a better understanding of the world from historical analogies. Second, my methodological argument proposes a frame of guiding questions for such discussions. These address the repertoire from which we select historical interpretations for analogies, the manner in which we interpret them, the similarities and differences between the past and present phenomena that the analogy compares, and the new insights that this comparison generates. Third, I employ these questions to put under scrutiny the historical analogies that the protagonists of the American Empire use to make their case for the supposedly benign American imperialism.
In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. Here we report the crystal structure of a complex between Imp4 and a short helical element of Mpp10 to a resolution of 1.88 Å. Furthermore, we extend the interaction network of Mpp10 and characterize two novel interactions. Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome.
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