Articles in 2023

Pseudouridine (Ψ) is an important modification in RNA biology and mRNA vaccine. A method called PRAISE was developed via selective labeling of Ψ by bisulfite to induce nucleotide deletion signature during reverse transcription, thus realizing quantitative assessment of the Ψ landscape in the human transcriptome.

Koller et al. determined structures of the O-glycosylated antimicrobial peptide drosocin from Drosophila melanogaster in complex with the bacterial ribosome, revealing the mechanism by which drosocin inhibits the termination phase of protein synthesis.

The antimicrobial peptide Drosocin encoded in the fruit fly genome inhibits bacterial translation by stalling the ribosomes at stop codons, sequestering class 1 release factors and inducing stop codon readthrough. Comprehensive mutational analysis reveals key activity determinants of Drosocin.

Profiling the resistance landscape to PRC2 inhibitors in EZH2-mutant lymphoma with CRISPR-suppressor scanning reveals drug addiction mutations and a repressive methylation ceiling. Surpassing the ceiling with SETD2 inhibition halts lymphoma growth.

An approach using glucose tracers and labeling of proline metabolites is applied to assess compartmentalized NADPH fluxes. The results show that NADPH fluxes in the cytosol and mitochondria are independently regulated, with no evidence of a shuttle.

Zhu et al. show how the growth-rate-dependent gene expression reshapes the landscape of cell-fate determination and highlight that expression capacities of genes have unbalanced response to growth variations.

Applying thermal proteome profiling to acute B cell childhood leukemia cell lines combined with deep peptide fractionation and a graph-based clustering algorithm allows inference of functional proteoform groups and their association with drug response.

Live-cell HRMAS NMR spectroscopy and genome-scale metabolic modeling enable high-resolution analysis of dynamic, anaerobic metabolism in Clostridioides difficile, identifying the confluence of carbohydrate and amino acid fermentations for alanine synthesis.

Kim et al. used directed evolution methods to identify a high-fidelity SpCas9 variant, Sniper2L, which exhibits high general activity but maintains high specificity at a large number of target sites.

The authors show modular functionality of TetR-like proteins in mammalian cells, separating the protein–DNA and the protein–protein interaction. This allows for engineered ON- and OFF-type responses to stimuli, higher order and multi-input logics.

A chemically controlled Cas9 switch offers a simple, general approach to temporal control of Cas9 effectors, including transcriptional activators, base editors and a prime editor. Chemically controlled base editors revealed bystander editing kinetics.

Using an integrated metabologenomics approach, the biosynthetic pathway for the pestalamides is revealed and over 200 high-confidence targets are identified for future studies.

Integrated phenotypic screening and activity-based protein profiling identifies small molecules that decrease the expression of oncogenic transcription factors and suppress cancer cell growth by covalently targeting the RNA-binding protein NONO.

Bifidobacterium bifidum is a member of the human gut microbiome. A new report demonstrates that it can degrade sulfated mucin O-glycans in vivo, and a GH20 sulfoglycosidase possessing a novel GlcNAc-6S-specific carbohydrate-binding module plays a pivotal role.

A first-in-class covalent inhibitor of creatine phosphagen energetics was developed that induced toxicity in creatine kinase-dependent AML cell lines and regulated proinflammatory cytokine production in macrophages.

In contrast to dsDNA phages where multiple genes are involved in programmed host lysis, ssRNA Fiersviridae phages require only a single gene. Here, genome-wide host suppressors of diverse single-gene lysis systems are identified using a high-throughput genetic screen.

Yu et al. identified sulfation modification that occurs on the tyrosine 99 residue of histone H3 (H3Y99sulf) and which is installed by histone sulfotransferase SULT1B1 and regulates gene transcription by recruiting PRMT1.

Spangler et al. used a substrate inhibitor covalent conjugate strategy to solve cryo-EM structures of nucleosomes in complex with the lysine demethylase KDM2, which demonstrates that KDM2A, but not its closely related paralog, KDM2B, anchors to the acidic patch to direct histone H3K36-specific demethylation.

Development of a generalized method for dual site-specific incorporation of nonnatural photocaged and photoreactive amino acids into proteins expressed in live cells enabled engineering of a photoreactive photoactive antibody fragment.

The function of a poorly characterized transmembrane protein, TMEM164, was annotated by integrated genetic dependency mapping, AlphaFold2 structural modeling and lipidomics as an acyltransferase that generates ferroptotic C20:4 ether phospholipids.