Coilin

A novel monoacylglycerol, 7.10 MAG, has been produced for use in the in meso (lipid cubic phase) crystallization of membrane proteins and complexes. 7.10 MAG differs from monoolein, the most extensively used lipid for in meso crystallization, in that it is shorter in chain length by one methylene and its cis olefinic bond is two carbons closer to the glycerol headgroup. These changes in structure alter the phase behavior of the hydrated lipid and the microstructure of the corresponding mesophases formed. Temperature-composition phase diagrams for 7...

Rare recessive variants in the human VRK1 gene are associated with several motor neuron diseases (MND), such as amyotrophic lateral sclerosis, spinal muscular atrophy, or distal hereditary motor neuropathies (dHMN). A case with dHMN carrying two novel VRK1 gene variants, expressing Leu200Pro (L200P) and Arg387His (R387H) variant proteins, identified that these protein variants are functionally different. The Leu200Pro variant shares with several variants in the catalytic domain the loss of the kinase activity on different substrates, such as histones, p53, or coilin...

Colorectal cancer (CRC) poses a significant challenge in terms of treatment due to the prevalence of radiotherapy resistance. However, the underlying mechanisms responsible for radio-resistance in CRC have not been thoroughly explored. This study aimed to shed light on the role of human coilin interacting nuclear ATPase protein (hCINAP) in radiation-resistant HT-29 and SW480 CRC cells (HT-29-IR and SW480-IR) and investigate its potential implications. Firstly, radiation-resistant CRC cell lines were established by subjecting HT-29 and SW480 cells to sequential radiation exposure...

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children and adolescents. Respecting the age of the patients and the tumor aggressiveness, investigation of the molecular mechanisms of RMS tumorigenesis is directed toward the identification of novel therapeutic targets. To contribute to a better understanding of the molecular pathology of RMS, we investigated ankyrin repeat domain 1 (ANKRD1), designated as a potential marker for differential diagnostics. In this study, we used three RMS cell lines (SJRH30, RD, and HS-729) to assess its expression profile, intracellular localization, and turnover...

Liquid-liquid phase separation is the key process underlying formation of membrane-less compartments in cells. A highly dynamic cellular body with rapid component exchange is Cajal body (CB), which supports the extensive compositional dynamics of the RNA splicing machinery, spliceosome. Here, we select an arginine-glycine (RG)-rich segment of coilin, the major component of CB, establish its RNA-induced phase separation, and through combined use of nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) probes, interrogate its dynamics within the crowded interior of formed droplets...

The mechanical damage of plant tissues leads to the activation of methanol production and its release into the atmosphere. The gaseous methanol or vapors emitted by the damaged plant induce resistance in neighboring intact plants to bacterial pathogens but create favorable conditions for viral infection spread. Among the Nicotiana benthamiana methanol-inducible genes (MIGs), most are associated with plant defense and intercellular transport. Here, we characterize NbMIG21 , which encodes a 209 aa protein (NbMIG21p) that does not share any homology with annotated proteins...

BACKGROUND: Most government efforts to control the COVID-19 pandemic revolved around non-pharmaceutical interventions (NPIs) and vaccination. However, many respiratory diseases show distinctive seasonal trends. In this manuscript, we examined the contribution of these three factors to the progression of the COVID-19 pandemic. METHODS: Pearson correlation coefficients and time-lagged analysis were used to examine the relationship between NPIs, vaccinations and seasonality (using the average incidence of endemic human beta-coronaviruses in Sweden over a 10-year period as a proxy) and the progression of the COVID-19 pandemic as tracked by deaths; cases; hospitalisations; intensive care unit occupancy and testing positivity rates in six Northern European countries (population 99...

PURPOSE: Platinum-based drugs are cytotoxic drugs commonly used in cancer treatment. They cause DNA damage, effects of which on chromatin and cellular responses are relatively well described. Yet, the nuclear stress responses related to RNA processing are incompletely known and may be relevant for the heterogeneity with which cancer cells respond to these drugs. Here, we determine the type and extent of nuclear stress responses of prostate cancer cells to clinically relevant platinum drugs...

MicroRNAs (miRNAs) are a class of noncoding RNAs that regulate gene expression. An important step in miRNA biogenesis occurs when primary miRNAs are bound and cleaved by the microprocessor to generate precursor miRNAs. Regulation at this step is essential and one such regulator includes m6A RNA methylation, an RNA modification found on primary miRNAs that is installed by METTL3 and bound by hnRNPA2B1. Our lab has recently discovered that the Cajal body marker protein coilin also participates in miRNA biogenesis and hypothesized that coilin may be influencing miRNA biogenesis through m6A RNA methylation...

In 2021, Campylobacteriosis was the main gastrointestinal disease in the European Union since 2007 according to the European Centre for Disease Prevention and Control. In the Republic of Ireland, the incidence of the disease is particularly high with approximately 3,000 cases per annum, raising significant concerns for national health authorities with an expected increase in the number of cases in the light of climate change. The current study sought to assess the spatio-temporal patterns of campylobacteriosis in the Republic of Ireland using 20,391 cases from January 2011 to December 2018...

Spinal muscular atrophy is an autosomal recessive neuromuscular disease caused by mutations in the multifunctional protein Survival of Motor Neuron, or SMN. Within the nucleus, SMN localizes to Cajal bodies, which are associated with nucleoli, nuclear organelles dedicated to the first steps of ribosome biogenesis. The highly organized structure of the nucleolus can be dynamically altered by genotoxic agents. RNAP1, Fibrillarin, and nucleolar DNA are exported to the periphery of the nucleolus after genotoxic stress and, once DNA repair is fully completed, the organization of the nucleolus is restored...

PURPOSE: Postoperative atrial fibrillation (POAF) has an incidence of 20-60% in cardiac surgery. The Society of Cardiovascular Anesthesiologists and the European Association of Cardiothoracic Anaesthesiology Practice Advisory have recommended postoperative beta blockers and amiodarone for the prevention of POAF. By employing quality improvement (QI) strategies, we sought to increase the use of these agents and to reduce the incidence of POAF among our patients undergoing cardiac surgery...

Cajal bodies (CBs) are major sub-nuclear structures in most eucaryotic cells. In human adenovirus 5 (Ad5) infection, CBs are reorganized into microfoci in the late phase of infection. Here we show that many CB protein components (p80-coilin, SMN-1, and WRAP53) remained stable throughout most of the infectious cycle of Ad type 5 (Ad5) in human A549 epithelial cells, even when CBs were reorganized into microfoci. Reduction of p80-coilin expression by RNA interference resulted in significant reductions in the levels of early (E1A, E2A-DBP), intermediate (pIX and IVa2), and late (L1-IIIa, L2-penton base, L3-hexon, L4-100K, and L5-fiber) proteins in Ad5-infected A549 cells...

The nucleus of higher eukaryotes contains a number of structures that concentrate specific biomolecules and play distinct roles in nuclear metabolism. In recent years, the molecular mechanisms controlling their formation have been intensively studied. In this brief review, I focus on coilin and Cajal bodies. Coilin is a key scaffolding protein of Cajal bodies that is evolutionarily conserved in metazoans. Cajal bodies are thought to be one of the archetypal nuclear structures involved in the metabolism of several short non-coding nuclear RNAs...

Coilin is a scaffold protein essential for the structure of Cajal bodies, which are nucleolar-associated, nonmembranous organelles that coordinate the assembly of nuclear ribonucleoproteins (RNPs) including spliceosomal snRNPs. To study coilin function in plants, we conducted a genetic suppressor screen using a coilin (coi1) mutant in Arabidopsis thaliana and performed an immunoprecipitation-mass spectrometry analysis on coilin protein. The coi1 mutations modify alternative splicing of a GFP reporter gene, resulting in a hyper-GFP phenotype in young coi1 seedlings relative to the intermediate wild-type level...

Bacterial lipoproteins (BLPs) decorate the surface of membranes in the cell envelope. They function in membrane assembly and stability, as enzymes, and in transport. The final enzyme in the BLP synthesis pathway is the apolipoprotein N -acyltransferase, Lnt, which is proposed to act by a ping-pong mechanism. Here, we use x-ray crystallography and cryo-electron microscopy to chart the structural changes undergone during the progress of the enzyme through the reaction. We identify a single active site that has evolved to bind, individually and sequentially, substrates that satisfy structural and chemical criteria to position reactive parts next to the catalytic triad for reaction...

The nucleolus and Cajal bodies (CBs) are sub-nuclear domains with well-known roles in RNA metabolism and RNA-protein assembly. However, they also participate in other important aspects of cell functioning. This study uncovers a previously unrecognised mechanism by which these bodies and their components regulate host defences against pathogen attack. We show that the CB protein coilin interacts with poly(ADP-ribose) polymerase 1 (PARP1), redistributes it to the nucleolus and modifies its function, and that these events are accompanied by substantial increases in endogenous concentrations of salicylic acid (SA), activation of SA-responsive gene expression and callose deposition leading to the restriction of tobacco rattle virus (TRV) systemic infection...

Since the start of the COVID-19 pandemic in early 2020, governments around the world have adopted an array of measures intended to control the transmission of the SARS-CoV-2 virus, using both pharmaceutical and non-pharmaceutical interventions (NPIs). NPIs are public health interventions that do not rely on vaccines or medicines and include policies such as lockdowns, stay-at-home orders, school closures, and travel restrictions. Although the intention was to slow viral transmission, emerging research indicates that these NPIs have also had unintended consequences for other aspects of public health...

Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men. TDRD1, a germ cell-specific gene, is erroneously expressed in more than half of prostate tumors, but its role in prostate cancer development remains elusive. In this study, we identified a PRMT5-TDRD1 signaling axis that regulates the proliferation of prostate cancer cells. PRMT5 is a protein arginine methyltransferase essential for small nuclear ribonucleoprotein (snRNP) biogenesis. Methylation of Sm proteins by PRMT5 is a critical initiation step for assembling snRNPs in the cytoplasm, and the final snRNP assembly takes place in Cajal bodies in the nucleus...

Spinal muscular atrophy is the leading genetic cause of infant mortality and results from depleted levels of functional survival of motor neuron (SMN) protein by either deletion or mutation of the SMN1 gene. SMN is characterized by a central TUDOR domain, which mediates the association of SMN with arginine methylated (Rme ) partners, such as coilin, fibrillarin, and RNA pol II (RNA polymerase II). Herein, we biochemically demonstrate that SMN also associates with histone H3 monomethylated on lysine 79 (H3K79me1 ), defining SMN as not only the first protein known to associate with the H3K79me1 histone modification but also the first histone mark reader to recognize both methylated arginine and lysine residues...