Design, synthesis, and screening of an RNA optimized fluorinated fragment library.

Fragment-based screening is an efficient method for early-stage drug discovery. In this study, we aimed to create a fragment library optimized for producing high hit rates against RNA targets. RNA has historically been an underexplored target, but recent research suggests potential for optimizing small molecule libraries for RNA binding.

ThrRS-Mediated Translation Regulation of the RNA Polymerase III Subunit RPC10 Occurs through an Element with Similarity to Cognate tRNA ASL and Affects tRNA Levels.

Aminoacyl tRNA synthetases (aaRSs) are a well-studied family of enzymes with a canonical role in charging tRNAs with a specific amino acid. These proteins appear to also have non-canonical roles, including post-transcriptional regulation of mRNA expression. Many aaRSs were found to bind mRNAs and regulate their translation into proteins.

Comprehensive characterization of mRNAs associated with yeast cytosolic aminoacyl-tRNA synthetases.

Aminoacyl-tRNA synthetases (aaRSs) are a conserved family of enzymes with an essential role in protein synthesis: ligating amino acids to cognate tRNA molecules for translation. In addition to their role in tRNA charging, aaRSs have acquired non-canonical functions, including post-transcriptional regulation of mRNA expression. Yet, the extent and mechanisms of these post-transcriptional functions are largely unknown.

RNA modifications as a common denominator between tRNA and mRNA.

Recent studies underscore RNA modifications as a novel mechanism to coordinate expression and function of different genes. While modifications on the sugar or base moieties of tRNA are well known, their roles in mRNA regulation are only starting to emerge. Interestingly, some modifications are present in both tRNA and mRNA, and here we discuss the functional significance of these common features.

Pseudouridine-mediated translation control of mRNA by methionine aminoacyl tRNA synthetase.

Modification of nucleotides within an mRNA emerges as a key path for gene expression regulation. Pseudouridine is one of the most common RNA modifications; however, only a few mRNA modifiers have been identified to date, and no one mRNA pseudouridine reader is known. Here, we applied a novel genome-wide approach to identify mRNA regions that are bound by yeast methionine aminoacyl tRNAMet synthetase (MetRS).

Localization and RNA Binding of Mitochondrial Aminoacyl tRNA Synthetases.

Mitochondria contain a complete translation machinery that is used to translate its internally transcribed mRNAs. This machinery uses a distinct set of tRNAs that are charged with cognate amino acids inside the organelle. Interestingly, charging is executed by aminoacyl tRNA synthetases (aaRS) that are encoded by the nuclear genome, translated in the cytosol, and need to be imported into the mitochondria.

Expanding the CRISPR/Cas9 Toolbox for Gene Engineering in S. cerevisiae.

The yeast S. cerevisiae serves as a model organism for many decades. Numerous molecular tools have been developed throughout the years to engineer its genome.

RNA mimicry in post-transcriptional regulation by aminoacyl tRNA synthetases.

Aminoacyl tRNA synthetases (aaRS) are well studied for their roles in tRNA charging with cognate amino acid. Nevertheless, numerous lines of evidence indicate that these proteins have roles other than tRNA charging. These include coordination of cellular signaling cascades, induction of cytokines outside the cell and transcription regulation.

mRNA association by aminoacyl tRNA synthetase occurs at a putative anticodon mimic and autoregulates translation in response to tRNA levels.

Aminoacyl-tRNA synthetases (aaRSs) are well studied for their role in binding and charging tRNAs with cognate amino acids. Recent RNA interactome studies had suggested that these enzymes can also bind polyadenylated RNAs. Here, we explored the mRNA repertoire bound by several yeast aaRSs.