EJC core component MLN51 interacts with eIF3 and activates translation.

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.

An Objective Approach to Identify Priority Rare Diseases for the Development of Solutions Reducing the Diagnostic Delay Based on French Data.

A 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 they are not only numerous but also extremely diverse in their expression and cause. This generates a long lag time between first symptoms and diagnosis, unanimously thought to be unacceptably long in many cases, and amenable to improvement. Digital technologies offer new 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). The approach presented here aims at proposing an objective way of defining a subset of "priority" RD to focus on for the development and test of new solutions to reduce the time to diagnosis. An approach which is relevant not only when developing and testing new digital solutions but also organizational solutions in the field of RDs. The priority RDs presented herein have been highlighted using two objective criteria: the existence of a well-defined and established standard of care management, defined as the availability of a medicinal product specifically targeting the disease; and / or the existence of authoritative clinical guidelines. Our approach, based on French data, led to the establishment of a list of 251 RD for which a delayed diagnosis would be especially detrimental for the patient. This work demonstrates the feasibility of identifying objectively a subset of RD at urgent needs for the development of solutions to reduce the delay to diagnosis, if choices have to be made, based on publicly and well-established available data. The proposed list needs to be updated and adapted to the local situation, and validated by experts to establish if the delay to diagnosis can be reduced.

3,5,7-Tripropyl-1-aza-adamantane-4,6,10-triol.

The title compound, C(18)H(33)NO(3), was prepared according to a highly diastereoselective hydrogenation procedure from 3,5,7-triallyl-1-aza-adamantane-4,6,10-trione. The crystal structure of the title compound contains two crystallographically independent mol-ecules (Z' = 2), which are linked by inter-molecular hydrogen bonding into chains. In contrast to the aza-adamantanones, the aza-adamantanetriol core of the title compound does not show any particular C-C bond elongation.