Farhangmehr et al. investigate functions of highly conserved intronic sequences in cell fitness using a CRISPR-based deletion screen. Deletions in FNBP4 intron lead to changes in p53 pathway genes. De...

Universität Greifswald

Protein biogenesis is a stress- and error-sensitive process that can lead to nascent protein misfolding and aggregation, challenging cellular proteostasis. Co-translational ubiquitination (CTU) is a c...

Schindler et al. report that RNA-binding proteins undergo widespread S-nitrosylation at evolutionarily conserved sites. S-nitrosylation of the master splicing regulator PTBP1 alters RNA-binding properties to reprogram the transcriptome and proteome. Nitric oxide thereby coordinates gene and protein regulation in cellular physiology and disease.

Biochemical, structural and cell biological analyses reveal that UAP56 (DDX39B) assembles with a TREX-2–like module that redirects non-functional polyadenylated RNAs from export to degradati...

Many long noncoding RNA–DNA binding peaks detected using common assays arise from technical artifacts.

Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organis...

Wei et al. demonstrate that 28S rRNA expansion segments are critical for multilayered nucleolar architecture formation through multivalent RNA-RNA interactions. Expansion segments from tripartite-nucleolus species confer enhanced multivalency of 28S rRNA, and transferring these segments across species is sufficient to induce nucleolar-like layered structures in vitro.

Ma et al. show that stress-induced, high-luminal Ca2+ ER sheets are selectively degraded by autophagy (ER-phagy), which requires the concerted actions of FAM134B and lipidated LC3. The ER-localized channels PIEZO1 and TRPV1 mediate Ca2+ release from these ER subdomains, triggering the formation of FIP200 puncta to initiate autophagosome assembly.

Nuclear speckles support the splicing of levelled exon–intron architecture transcripts, and their evolution shaped genome organization in amniotes.

Biological processes rely on finely tuned homo- and heteromeric interactions between (biomacro)molecules. The strength of an interaction, typically given by the dissociation constant (KD), plays a crucial role in basic research and must be monitored throughout the development of drugs and agrochemicals. An ideal method for KD determination is applicable to various analytes with a large range of affinities, tolerates complex matrix compositions, does not require labeling, and simultaneously provides information on the structural integrity of the binding partners. Native mass spectrometry meets these criteria but typically struggles with homooligomeric complexes due to overlapping mass signals. To overcome this, we resolve monomer/dimer contributions to overlapping MS-peaks by separately analyzing the charge state distribution of each oligomeric species via sample dilution and covalent cross-linking. Following this approach, we show that quantitative laser-induced liquid bead ion desorption mass spectrometry (qLILBID-MS) accurately captures the affinities of Bovine Serum Albumin (BSA) and chemically induced dimers of Tryparedoxin (Tpx), an oxidoreductase from human pathogenic Trypanosoma brucei parasites, with various molecular glues and homodimer affinities. Conveniently, qLILBID-MS requires a fraction of sample used by other methods such as isothermal titration calorimetry (ITC) and yields previously inaccessible protein homodimer KDs in the high micromolar range, which allowed us to monitor the gradual decrease in homodimer affinity via mutation of crucial dimer interface contacts. Overall, qLILBID-MS is a sensitive, robust, fast, scalable, and cost-effective alternative to quantify protein/protein interactions, that can accelerate contemporary drug discovery workflows, e.g. the efficient screening for proximity inducing molecules like proteolysis targeting chimera (PROTACs) and molecular glues.

Nature - Researchers simulated nearly every molecule in a bacterial cell — and then watched the cell grow and reproduce.

Abstract. Pancrustacean Dscam1 genes encode 2 000–120 000 distinct isoforms via mutually exclusive splicing; however, the underlying regulatory mechanisms

Junior researchers are more likely to embrace preprints; grant reviewers and hiring committees express doubts