In recent years there have been major advances with respect to the identification of the protein components and mechanisms of microRNA (miRNA) mediated silencing. However, the complete and precise repertoire of components and mechanism(s) of action remain to be fully elucidated. Herein we reveal the identification of a family of three LIM domain-containing proteins, LIMD1, Ajuba and WTIP (Ajuba LIM proteins) as novel mammalian processing body (P-body) components, which highlight a novel mechanism of miRNA-mediated gene silencing. Furthermore, we reveal that LIMD1, Ajuba, and WTIP bind to Ago1/2, RCK, Dcp2, and eIF4E in vivo, that they are required for miRNA-mediated, but not siRNA-mediated gene silencing and that all three proteins bind to the mRNA 5′ m ⁷ GTP cap–protein complex. Mechanistically, we propose the Ajuba LIM proteins interact with the m ⁷ GTP cap structure via a specific interaction with eIF4E that prevents 4EBP1 and eIF4G interaction. In addition, these LIM-domain proteins facilitate miRNA-mediated gene silencing by acting as an essential molecular link between the translationally inhibited eIF4E-m ⁷ GTP-5 ^′ cap and Ago1/2 within the miRISC complex attached to the 3′-UTR of mRNA, creating an inhibitory closed-loop complex.

Ammonia plays a crucial role in agriculture and chemical engineering, and acts as a promising carbon-free transportation fuel. Catalysts design is deemed as a key to solve the restriction of energy-intensive Haber–Bosch process of ammonia production. With the development of computational modeling, computation-aided catalyst design serves as one important driving force for material innovation, saving a lot of experimental efforts based on trial and error. Computational modeling not only provides fundamental mechanistic insights into the reaction with great details regarding adsorbate geometries, electronic structures, and elementary-step energies, but also expedites the material discovery with descriptor-based catalyst design, core of which is the establishment of thermo/kinetic scaling relations. In this review, we present firstly the mechanistic understanding of ammonia synthesis and transition state scaling relations developed on pure transition-metal catalysts. We then summarize catalysts design strategies guided by alloy, size, and magnetic effects with the goal of breaking the limitations set by scaling relations to achieve better catalytic performance. Finally, future opportunities and challenges associated with computation design of optimal catalysts for ammonia synthesis are outlined.