Experience-dependent neural plasticity, learning, and memory in the era of epitranscriptomics.

In this short review, we highlight recent findings in the emerging field of epitranscriptomic mechanisms and discuss their potential role in neural plasticity, learning and memory. These include the influence of RNA modifications on activity-induced RNA structure states, RNA editing and RNA localization, and how qualitative state changes in RNA increase the functional diversity and information-carrying capacity of RNA molecules. We predict that RNA modifications may be just as important for synaptic plasticity and memory as quantitative changes in transcript and protein abundance, but with the added advantage of not being required to signal back to the nucleus, and therefore better suited to be coordinated with the temporal dynamics of learning.

Photo-controlled cell-specific metabolic labeling of RNA.

Elucidating gene expression programs within a cell-specific manner is a grand challenge for biologists. Harder still is the ability to have kinetic control over such experiments. Metabolic labeling with bioorthogonally-functionalized metabolic intermediates provides a means to profile RNA expression in a cell-specific manner, but there is still a lack of kinetic resolution. Herein we present the synthesis and evaluation of photocaged metabolic uracil intermediates. We compare the photo-decaging properties and demonstrate their utility in metabolic labeling experiments in a cell-specific manner. We anticipate that our approach will have far-reaching impact as it provides control over tagging of nascent RNA.

Molecular targets of aspirin and cancer prevention.

Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug.