Cell Chemical Biology最新文献

In early October, the Nobel Prizes will honor groundbreaking discoveries. After the anticipated recognition of Katalin Karikó and Drew Weissman in 2023 for the development of RNA modifications that enabled the SARS-CoV-2 mRNA vaccine, we eagerly consider the next topics to be awarded. In the September 30^th anniversary special issue of Cell Chemical Biology, we ask researchers from a range of backgrounds, what topic do you think deserves the next Nobel Prize in chemistry or in physiology or medicine, and why?

Synthetic-based fluorescent chemosensors and protein-based fluorescent biosensors are two well-established classes of tools for visualizing and monitoring biological processes in living tissues. Chemigenetic sensors, created using a combination of both synthetic parts and protein parts, are an emerging class of tools that aims to combine the strengths, and overcome the drawbacks, of traditional chemosensors and biosensors. This review will survey the landscape of strategies used for fluorescent chemigenetic sensor design. These strategies include: attachment of synthetic elements to proteins using in vitro protein conjugation; attachment of synthetic elements to proteins using autonomous protein labeling; and translational incorporation of unnatural amino acids.

Biomolecular condensates are dynamic membraneless organelles that compartmentalize proteins and RNA molecules to regulate key cellular processes. Diverse RNA species exert their effects on the cell by their roles in condensate formation and function. RNA abnormalities such as overexpression, modification, and mislocalization can lead to pathological condensate behaviors that drive various diseases, including cancer, neurological disorders, and infections. Here, we review RNA’s role in condensate biology, describe the mechanisms of RNA-induced condensate dysregulation, note the implications for disease pathogenesis, and discuss novel therapeutic strategies. Emerging approaches to targeting RNA within condensates, including small molecules and RNA-based therapies that leverage the unique properties of condensates, may revolutionize treatment for complex diseases.

RNA molecules undergo dynamic chemical modifications in response to various external or cellular stimuli. Some of those modifications have been demonstrated to post-transcriptionally modulate the RNA transcription, localization, stability, translation, and degradation, ultimately tuning the fate decisions and function of mammalian cells, particularly T cells. As a crucial part of adaptive immunity, T cells play fundamental roles in defending against infections and tumor cells. Recent findings have illuminated the importance of RNA modifications in modulating T cell survival, proliferation, differentiation, and functional activities. Therefore, understanding the epi-transcriptomic control of T cell biology enables a potential avenue for manipulating T cell immunity. This review aims to elucidate the physiological and pathological roles of internal RNA modifications in T cell development, differentiation, and functionality drawn from current literature, with the goal of inspiring new insights for future investigations and providing novel prospects for T cell-based immunotherapy.

Prephenate decarboxylases are a small family of enzymes which initiate a specialized divergence from the shikimate pathway, where prephenate (2) is decarboxylated without aromatization. In addition to effecting a challenging chemical transformation, prephenate decarboxylases have been implicated in the production of rare specialized metabolites, sometimes directly constructing bioactive warheads. Many of the biosynthetic steps to natural products derived from prephenate decarboxylases remain elusive. Here, we review prephenate decarboxylase research thus far and highlight natural products that may be derived from biosynthetic pathways involving prephenate decarboxylases. We also highlight commonly encountered challenges in the structure elucidation of these natural products. Prephenate decarboxylases are a gateway into understudied biosynthetic pathways which present a high potential for the discovery of novel and bioactive natural products, as well as new biosynthetic enzymes.