Is there any intron sliding in mammals?

Abstract Background Eukaryotic protein-coding genes consist of exons and introns. Exon–intron borders are conserved between species and thus their changes might be observed only on quite long evolutionary distances. One of the rarest types of change, in which intron relocates over a short distance, is called "intron sliding", but the reality of this event has been debated for a long time. The main idea of a search for intron sliding is to use the most accurate genome annotation and genome sequence, as well as high-quality transcriptome data. We applied them in a search for sliding introns in mammals in order to widen knowledge about the presence or absence of such phenomena in this group. Results We didn’t find any significant evidence of intron sliding in the primate group (human, chimpanzee, rhesus macaque, crab-eating macaque, green monkey, marmoset). Only one possible intron sliding event supported by a set of high quality transcriptomes was observed between EIF1AX human and sheep gene orthologs. Also, we checked a list of previously observed intron sliding events in mammals and showed that most likely they are artifacts of genome annotations and are not shown in subsequent annotation versions as well as are not supported by transcriptomic data. Conclusions We assume that intron sliding is indeed a very rare evolutionary event if it exists at all. Every case of intron sliding needs a lot of supportive data for detection and confirmation

Analysis of Predicted Amino Acid Sequences of Diatom Microtubule Center Components

Diatoms synthesize species-specific exoskeletons inside cells under the control of the cytoskeleton and microtubule center. Previous studies have been conducted with the visualization of the microtubule center; however, its composition has not been studied and reliably established. In the present study, several components of MTOC in diatoms, GCP (gamma complex proteins), Aurora A, and centrins have been identified. Analysis of the predicted amino acid sequences of these proteins revealed structural features typical for diatoms. We analyzed the conserved amino acids and the motives necessary for the functioning of proteins. Phylogenetic analysis of GCP showed that all major groups of diatoms are distributed over phylogenetic trees according to their systematic position. This work is a theoretical study; however, it allows drawing some conclusions about the functioning of the studied components and possible ways to regulate them

Deep Functional Profiling Facilitates the Evaluation of the Antibacterial Potential of the Antibiotic Amicoumacin

The global spread of antibiotic resistance is forcing the scientific community to find new molecular strategies to counteract it. Deep functional profiling of microbiomes provides an alternative source for the discovery of novel antibiotic producers and probiotics. Recently, we implemented this ultrahigh-throughput screening approach for the isolation of Bacillus pumilus strains efficiently producing the ribosome-targeting antibiotic amicoumacin A (Ami). Proteomics and metabolomics revealed essential insight into the activation of Ami biosynthesis. Here, we applied omics to boost Ami biosynthesis, providing the optimized cultivation conditions for high-scale production of Ami. Ami displayed a pronounced activity against Lactobacillales and Staphylococcaceae, including methicillin-resistant Staphylococcus aureus (MRSA) strains, which was determined using both classical and massive single-cell microfluidic assays. However, the practical application of Ami is limited by its high cytotoxicity and particularly low stability. The former is associated with its self-lactonization, serving as an improvised intermediate state of Ami hydrolysis. This intramolecular reaction decreases Ami half-life at physiological conditions to less than 2 h, which is unprecedented for a terminal amide. While we speculate that the instability of Ami is essential for Bacillus ecology, we believe that its stable analogs represent attractive lead compounds both for antibiotic discovery and for anticancer drug development

Proteogenomic characterization of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets. [Display omitted] •Proteogenomic characterization reveals the functional impact of genomic alterations•Phosphoproteomics uncovers putative therapeutic targets downstream of KRAS•Multiomics links endothelial cell remodeling and glycolysis to immune exclusion•Proteomics and glycoproteomics reveal candidates for early detection or intervention Comparative multiomic analyses of pancreatic ductal adenocarcinoma tumors with normal adjacent and pancreatic ductal tissues provide insight into genomic, proteomic, and immune dysregulation in driving disease