SEARCH · PubMed Health

Results for “Cytoplasmic Ribonucleoprotein Granules”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

12 recordsLinked to original sources

PubMed2024

MX2 forms nucleoporin-comprising cytoplasmic biomolecular condensates that lure viral capsids.

Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1.

Humans↗

PubMed2026

Dysregulated Ribonucleoprotein Granules Impair Mitochondrial Function in RBM20-Related Dilated Cardiomyopathy.

BACKGROUND: Pathogenic variants in RBM20 cause severe dilated cardiomyopathy. Loss-of-function variants disrupt splicing; neomorphic gain-of-function (GoF) variants also mislocalize RBM20 to cytoplasmic ribonucleoprotein granules and are associated with more aggressive disease. The mechanism by which RBM20 mislocalization drives cardiac dysfunction remains unknown. METHODS: We investigated the effects of Rbm20 GoF and loss-of-function (LoF) variants using proteomic profiling, protein solubility assays, mitochondrial respiration and calcium flux analyses, and ultrastructural imaging in mouse models. Human induced pluripotent stem cell-derived cardioids were used to validate variant-specific phenotypes. RESULTS: Rbm20 GoF, but not LoF, variants caused posttranscriptional downregulation of soluble mitochondrial proteins, including the calcium efflux regulator TMEM65 (transmembrane protein 65), and reduced solubility of mitochondrial membrane proteins. Electron microscopy revealed enlarged mitochondria with cristae disorganization. Functional assays confirmed impaired oxidative phosphorylation, reduced mitochondrial membrane potential, and abnormal calcium handling in Rbm20 GoF models. Human cardioids reproduced these findings, demonstrating that cytoplasmic mislocalization, rather than splicing deficiency, drives mitochondrial dysfunction. CONCLUSIONS: Cytoplasmic mislocalization of RBM20 disrupts mitochondrial function by reducing mitochondrial protein abundance, leading to oxidative phosphorylation failure and abnormal mitochondrial calcium handling. This mechanism distinguishes RBM20 GoF from LoF variants and may explain the more severe heart failure phenotype observed in patients with RBM20 GoF variants. These insights advance the mechanistic understanding of RBM20-related cardiomyopathy and identify mitochondrial mRNA/protein regulation as a key node in cardiac energetics.

cardiomyopathy, dilated↗

PubMed2026

Differential assembly of RNP granules via activation of distinct dsRNA sensors by adenovirus mutants.

Recognition of double-stranded RNA (dsRNA) triggers antiviral defense mediated by PKR and OAS3/RNase L pathways through translational arrest and RNA decay. This is accompanied by assembly of distinct cytoplasmic ribonucleoprotein (RNP) condensates termed stress granules (SGs) and RNase L-dependent bodies (RLBs). Here we show that adenovirus mutants engage distinct RNA-sensing pathways and promote differential assembly of cytoplasmic RNP granules. Infection with splicing-defective ∆E4 mutant leads to dsRNA accumulation and activation of both PKR and OAS3/RNase L, promoting formation of RLB-like granules. In contrast, mutants lacking virus-associated (VA) RNAs trigger PKR activation and assembly of SGs despite absence of detectable dsRNA. Proximity labeling proteomic analysis revealed distinct protein compositions of canonical SGs and RLBs, which were reflected in virus-induced granules. While ∆VA-induced granules were PKR-dependent, ∆E4 mutants induced RLB-like granules independently of PKR and RNase L. In cells lacking these sensors, granule assembly during ∆E4 infection coincided with translational arrest independent of eIF2α phosphorylation, indicating additional pathways linking nuclear dsRNA sensing to translational control and RNP granule assembly during viral infection. These findings provide novel insights into how distinct dsRNA sensors modulate translation and RNP condensates in response to stress.

RNA, Double-Stranded↗

PubMed1979

Ultrastructural and autoradiographic study of the effects of bleomycin on the interphase nucleus of cultured normal cells.

Primary cultures of hepatocytes and epithelial endometrial cells were treated with bleomycin (10 to 200 microgram/ml) for 30 to 300 min. Structural changes were studied with a staining method which contrasts ribonucleoproteins. The earliest visible alteration was the accumulation of perichromatin granules in association with the nucleolus. This disturbance was frequently accompanied by modifications in the nucleolar architecture. After larger treatments, the most striking changes were nucleolar segregation and the appearance of spherical clear bodies in the nucleolus. In the extranucleolar area, a remarkable diminution of ribonucleoprotein fibrils and clustering of interchromatin granules were observed. Functional disturbances in the synthesis and transporting of RNA to the cytoplasm were studied by high-resolution quantitative autoradiography after labeling with tritiated uridine. Bleomycin produces a strong inhibition of RNA synthesis in nucleolar and extranucleolar areas. Important decreases of [3H]uridine incorporation were observed as early as 30 min after the administration of drug. Alterations of processing and/or transporting of RNA to the cytoplasm were found after treatments with bleomycin (100 microgram/ml) for 30 to 300 min. It is suggested that the diminution of ribonucleoprotein fibrils is related to the inhibition of RNA synthesis while the accumulation of perichromatin granules is connected to alteration of the transporting and/or processing.

Animals↗

PubMed1978

Cytology of the superficial keratinised cells in experimental keratitis sicca.

Keratoconjunctivitis sicca was produced in 2 rabbits by the surgical extirpation of the tear-secreting glands and the nictitating membrane in one eye. Flat mounts of the superficial corneal epithelium were prepared by the in vivo replica technique. Histomorphological and cytological studies of the keratinised cells showed the irregularly arranged, crumpled and piled-up cells. The cells contained coarse granular and fibrillar material in the cytoplasm and large granules in the nuclei. The reaction for -S-S- bridges was positive in these cells. They showed birefringence under polarisation microscopy but possessed some ribonucleoproteins.

Animals↗

PubMed1977

Cytoplasmic aggregates in D-galactosamine induced liver injury.

D-galactosamine treatment leads to the formation of PAS-positive granules or aggregates in the cytoplasm of mouse liver cells. Ultrastructural observations show that the granules consist of particles surrounded by membranes of rough endoplasmic reticulum. Cytochemical results reveal that part of the particles is pronase-sensitive and amylase resistant, staining positively by the Thiéry silver proteinate method. The other part is stained positively by EDTA preferentional staining. According to the cyto-and histochemical results the granules consist of ribosomes and abnormal basic glycogen. The aggregates are removed from the cytoplasm mostly by lysosomal degradation.

Animals↗

PubMed1976

Some histochemical studies on the prostate, urethral and bulbourethral glands of the one-humped camel (Camelus dromedarius).

The histochemical localization of carbohydrates, ribonucleoproteins (RNA), lipids, some hydrolytic enzymes, succinate and lactate dehydrogenase and acetylcholinesterase were investigated in the prostate, urethral and bulbourethral glands of the camel. These glands probably secrete carbohydrate-protein complexes. In the bulbourethral glands, they are sulphated mucopolysaccharides. RNA was seen in the cytoplasm of the prostate and urethral glands. Neutral lipids were cytoplasmic and present in moderate amounts in the prostate and urethral glands and in traces, in the bulbourethral gland. Acid phosphatase-containing granules were abundant in the prostate, moderate in the urethral glands and in traces in the bulbourethral glands. Alkaline phosphatase was observed in the apical cytoplasm of the prostate and bulbourethral glands and in the ducts of the urethral glands. ATPase and adenosine 5-monophosphatase were seen in the basal laminae and interstitial tissue. In the urethral glands, adenosine 5-monophosphatase was distributed diffusely in the cytoplasm. Succinate dehydrogenase was seen in the urethral and bulbourethral glands. Varying degrees of lactate dehydrogenase activity was observed in all the glands. Acetylcholinesterase was confined to neural elements. The pars disseminata and the urethral glands were considered as two distinct glandular zones along the pelvic urethra. The significance of these histochemical results is discussed.

Acetylcholinesterase↗

PubMed1976

A cytological method for the simultaneous staining of nucleoproteids and some cathionic proteins.

A cytochemical method is suggested for the simultaneous and differential staining of cellular nucleoproteids [ribonucleoproteids (RNP) and desoxyribonucleoproteids (DNP)], as well as for the simultaneous contrast staining of some basic (arginine- and lysin-containing) proteins. The staining technique is based on DNA-denaturation procedures and the application of mixtures of basic dye--methylene blue and acid dyes--eosin or fast green at low concentrations. The combination of methylene blue with eosin is used for the staining of ribonucleoproteids (RNP) whereas methylene blue-fast green for the simultaneous detection of ribonucleoproteids and desoxyribonucleoproteids (RNP and DNP), as well as for the differential staining of nuclear DNP (after cold hydrolysis with 5 N HCl). The acid dyes eosin and fast green stain in pink resp. in green some cathionic proteins in the lysosomal (specific) granules of the neutrophilic and eosinophilic leucocytes in the cytoplasm of erythrocytes, and after cold hydrolysis in the cytoplasm of lymphocytes. A fluorescent variant of the method with sulfaflavin is also suggested for the fluorochromation of cytoplasmic cathionic granules in the luecocytes. Acid mucopolysaccharide components in the granules of basophilic leucocytes, tissue mastocytes and thrombocyres are stained intensively pink-violet (gamma-metachromatic). The possibilities for the application of the method in the quantitative analysis of blood and exfoliated cells, as well as for purpose of haematology, immunology and exfoliative cytology are discussed.

Arginine↗

PubMed1975

Masking of pleomorphic glycogen sites by methanolic uranyl acetate.

Rat liver tissue was fixed in 2.5% glutaraldehyde buffered with cacodylic acid (pH 7.3) for 2 hr, washed twice in buffer, and postfixed in 2% osmium tetroxide at 4 C for 1 hr. The tissue then was dehydrated, infiltrated with and embedded in Epon by routine procedures. The ultrathin sections from this tissue, when stained with spectroscopic grade methanol saturated with uranyl acetate (SMUA) for 1 min followed by aqueous lead citrate (PbCi) (Reynolds 1963) for 5 min at room temperature, showed a uniform staining of all major cellular components except glycogen. The SMUA appeared to be specific for ribonuceloprotein granules, rendering them more prominent in the cytoplasm due to the lack of glycogen staining. The question of glycogen removal from the sections due to SMUA treatment was evulated using various extractions and staining methods. It appeared that SMUA pretreatment alters the subsequent binding ability of lead salts, resulting in lack of glycogen staining, although it does not remove the glycogen from the sections.

Acetates↗

PubMed1979

Cytochemistry of nucleoproteids and some cathionic proteins in the peripheral blood leukocytes of patients with lung cancer.

In 40 patients with untreated lung cancer cytochemical studies of the peripheral blood leukocytes were conducted by means of a cytological method for the simultaneous staining of nucleoproteids (RNP and DNP) and some cathionic proteins (after Zvetkova and Zvetkov [60]). Changes were detected in the RNP cytoplasmic contents of lymphocytes, of which the most outstanding were the reduction and uneven distribution of RNP granules, their frequent extracellular expulsion by means of microclasmatoses, as well as changes in the staining of cathionic proteins of RNP accompanied by an increased nuclear chromatin condensation in the small and medium-sized lymphocytes. Parellel to reducing of the percentage of these cells in the peripheral blood of patients with advanced neoplastic disease an increased number of lymphoblastoid and monoblastoid cells is established with RNP diffusely stained, but reduced in quantity and localized in the cytoplasmic periphery and projections (compared to Downey type II atypical cells). By means of one of the variants of the method (modified type of Feulgen's reaction) a characteristic distribution and structuring of the nuclear chromatin is established in mono- and polymorphonuclear cells, most clearly expressed in the nuclei of monocytes and monoblastoid cells, as well as in nuclei of neutrophil granulocytes. In these cellular types a more specific nuclear modelling (microhypersegmentation) is observed resulting in multiple irregular nuclear projections on the nuclear surface, probably caused by subkaryolemal distribution of uneven chromatin thickenings. The changes are also recorded in the cathionic protein containing secondary cytoplasmic granules in granulocytes-neutrophils and eosinophils, probably associated with changes in the lysosomal and phagocytic functions of these cells in neoplastic diseases. The authors discuss the importance of the obtained results in connection with data on the participation of lymphocytes and neutrophils in the immune response to tumour antigenic stimuli during the course of the neoplastic process, as well as with data on the suppressive effect of antigenic (serum, viral) factors, possibly affecting the synthesis and the transport of cellular nucleoproteids (RNP and DNP) in leukocytes of cancer patients.

Blood Proteins↗

PubMed1978

Effects of ovariectomy and estradiol injection on nuclear structures of endometrial epithelial cells.

The changes of the rate of RNA synthesis produced by castration and estradiol injection on the surface endometrial cells of the rat are profited to study the variations in the number and size of nuclear ribonucleoprotein structures and in the disposition of chromatin. Two-dimensional measurements on sections contrasted with preferential procedures were employed to estimate the fraction of nuclear volume occupied by each element. Young adult rats in estrus are used as controls. 3 weeks after ovariectomy, the area fraction occupied by the nucleolus is reduced almost to a third of the control value, while the number of perichromatin granules per unit area of nucleus has significantly increased. A single injection of 20 microgram of estradiol produces a rapid decrease of the number of perichromatin granules to a fourth of the value of castrate animals, in 15-30 min, followed by a slow increase. Nucleolar area fraction begins to increase 2 h after estrogen administration and at 24 h it is higher than in controls. It is concluded that the changes of the nucleolar volume are due to the effects of estradiol on the synthesis of nucleolar RNA, while the variations of perichromatin granules are produced by the combination of the effect on extranucleolar RNA synthesis and on its processing and/or transporting to the cytoplasm. Both effects are independent and undergo different temporal courses.

Animals↗

PubMed2026

PTBP1 at the host-virus interface: mechanistic roles in viral RNA translation, replication, and immune modulation.

Viruses require the involvement of host RNA binding proteins for completion of important steps of their life cycle. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA-binding protein found ubiquitously which performs important regulatory functions like alternative splicing, RNA stability, RNA localization, and translation by virtue of its four RRMs and shuttling between nucleus and cytoplasm. There is increasing evidence showing that many viruses make use of such regulatory roles of PTBP1 to facilitate their gene expression and replication. This review describes the existing mechanistic knowledge about the PTBP1 functions during viral infection, paying attention to the role of PTBP1 in viral RNA translation, viral RNA genome replication, and regulation of host antiviral response. Special attention is paid to the regulation by PTBP1 of IRES-dependent translation of enteroviruses and hepatitis C virus, as well as to the PTBP1 contribution to RNA stabilization, long-distance RNA interactions, and genome cyclization of flaviviruses such as dengue virus and Japanese encephalitis virus. Recent data on the PTBP1 function in coronavirus RNA metabolism are discussed as well. Furthermore, the role of PTBP1 in being both proviral and antiviral is reviewed in terms of innate immunity signalling pathways, stress granule biology, and virus-host interaction. Finally, we will explore the possibility of PTBP1 being used as a host-directed antiviral drug target despite the hurdles in doing so considering its multifunctionality as an essential cellular RNA-binding protein.

Polypyrimidine Tract-Binding Protein↗