The multiprotein exon junction complex (EJC), deposited by the splicing machinery, is an important constituent of messenger ribonucleoprotein particles because it participates to numerous steps of the mRNA lifecycle from splicing to surveillance via nonsense-mediated mRNA decay pathway. By an unknown mechanism, the EJC also stimulates translation efficiency of newly synthesized mRNAs. Here, we show that among the four EJC core components, the RNA-binding protein metastatic lymph node 51 (MLN51) is a translation enhancer. Overexpression of MLN51 preferentially increased the translation of intron-containing reporters via the EJC, whereas silencing MLN51 decreased translation. In addition, modulation of the MLN51 level in cell-free translational extracts confirmed its direct role in protein synthesis. Immunoprecipitations indicated that MLN51 associates with translation-initiating factors and ribosomal subunits, and in vitro binding assays revealed that MLN51, alone or as part of the EJC, interacts directly with the pivotal eukaryotic translation initiation factor eIF3. Taken together, our data define MLN51 as a translation activator linking the EJC and the translation machinery.

BackgroundA timely diagnosis is a critical step to ensure a proper access to expert clinical management for patients. However, diagnosing rare diseases (RD) is a major challenge, as these diseases are extremely diverse in their expression, cause, semiology and nosology. Today, the development of digital technologies offers genuine opportunities for improving diagnosis and care in a sector with urgent needs. However, developing and testing digital solutions would only be possible for a limited number of Rare Diseases (RD). ResultsThe approach presented in this article aims at proposing an ethical and rational way of defining a subset of “priority” rare diseases to focus on, based on pathologies for which an established and effective standard of care management is defined. Two types of management were considered: the existence of a medicinal product specifically targeting the disease; and / or the existence of authoritative clinical guidelines in France. Our work led to the establishment of a list of 251 RD for which a delayed diagnosis would be especially detrimental. ConclusionIt remains now to establish whether the diagnosis of these RD is especially delayed, or not, before setting up targeted initiatives to reverse the situation. Clarifying choices when taking initiatives to develop solution in a field with so many unmet needs is an element of an ethical approach.

The title compound, C18H33NO3, was prepared according to a highly diastereoselective hydrogenation procedure from 3,5,7-triallyl-1-aza­adamantane-4,6,10-trione. The crystal structure of the title compound contains two crystallographically independent mol­ecules (Z′ = 2), which are linked by inter­molecular hydrogen bonding into chains. In contrast to the aza­adamantanones, the aza­adamantanetriol core of the title compound does not show any particular C—C bond elongation.