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Fernanda López-Moncada, Daniel Tapia, Nolberto Zuñiga, Eliana Ayarza, Julio López-Fenner, Carlo Alberto Redi, Soledad Berríos
We studied and compared the nucleolar expression or nucleoli from specific bivalents in spermatocytes of the standard Mus musculus domesticus 2n=40, of Robertsonian (Rb) homozygotes 2n = 24 and heterozygotes 2n = 32. We analyzed 200 nuclear microspreads of each specific nucleolar chromosome and spermatocyte karyotype, using FISH to identify specific nucleolar bivalents, immunofluorescence for both fibrillarin of the nucleolus and the synaptonemal complex of the bivalents, and DAPI for heterochromatin. There was nucleolar expression in all the chromosomal conditions studied...
February 6, 2019: Genes
Kjell E J Håkansson, Eveline A C Goossens, Stella Trompet, Eva van Ingen, Margreet R de Vries, Reginald V C T van der Kwast, Rasmus S Ripa, Jens Kastrup, Philipp J Hohensinner, Christoph Kaun, Johann Wojta, Stefan Böhringer, Saskia le Cessie, J Wouter Jukema, Paul H A Quax, A Yaël Nossent
Aims: We have shown that 14q32 microRNAs are highly involved in vascular remodeling and cardiovascular disease. However, the 14q32 locus also encodes 41 'orphan' small nucleolar RNAs (snoRNAs). We aimed to gather evidence for an independent role for 14q32 snoRNAs in human cardiovascular disease. Methods & Results: We performed a look-up of the 14q32 region within the dataset of a Genome Wide Association Scan (GWAS) in 5244 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)...
December 13, 2018: Cardiovascular Research
Aishwarya Iyer-Bierhoff, Nicolai Krogh, Peter Tessarz, Thomas Ruppert, Henrik Nielsen, Ingrid Grummt
Fibrillarin (FBL) is a dual-function nucleolar protein that catalyzes 2'-O methylation of pre-rRNA and methylation of histone H2A at glutamine 104 (H2AQ104me). The mechanisms that regulate FBL activity are unexplored. Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7. While reversible acetylation does not impact FBL-mediated pre-rRNA methylation, hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription...
December 11, 2018: Cell Reports
Btissame El Hassouni, Dzjemma Sarkisjan, J Chris Vos, Elisa Giovannetti, Godefridus J Peters
BACKGROUND: Inherent or acquired chemo resistance in cancer patients has been a perpetual limitation in cancer treatment. Expanding knowledge on essential cellular processes opens a new window for therapeutic targeting. Ribosome biogenesis is a process that shows potential due to its fundamental role in cell development and contribution to tumorigenesis as a result of its upregulation. Inhibiting components of ribosome biogenesis has been explored and has shown interesting results. Yet, an important key component, methyltransferase Fibrillarin (FBL), which influences both the abundance and composition of ribosomes, has not been exploited thus far...
December 3, 2018: Current Medicinal Chemistry
Sarah Naulikha Kituyi, Adrienne Lesley Edkins
Hop/STIP1 is a co-chaperone of Hsp70 and Hsp90 that regulates a number of cell biology processes via interactions with cellular proteins. Here we report a new relationship between Hop and the nuclear structural protein emerin in maintenance of nuclear morphology. Depletion or overexpression of Hop resulted in the reduction of emerin protein levels via proteasomal and lysosomal pathways. Co-immunoprecipitation assays confirmed that Hop and emerin are in a common complex, which could accommodate Hsp70 but not Hsp90, and that TPR2AB is required for the association...
December 9, 2018: Biochemical and Biophysical Research Communications
Jun Sung Seo, Piyarut Diloknawarit, Bong Soo Park, Nam-Hai Chua
Plant immune response is initiated upon the recognition of pathogen-associated molecular patterns such as elf18. Previously, we identified an Arabidopsis ELF18-INDUCED LONG NONCODING RNA 1 (ELENA1), as a positive transcriptional regulator of immune responsive genes. ELENA1 associated with Mediator subunit 19a (MED19a) to enhance enrichment of the complex on PATHOGENESIS-RELATED GENE 1 (PR1) promoter. In vitro and in vivo RNA-protein interaction experiments showed that ELENA1 can also interact with FIBRILLARIN 2 (FIB2)...
October 11, 2018: New Phytologist
Jue Zhang, Yin-Li Zhang, Long-Wen Zhao, Jing-Xin Guo, Jia-Li Yu, Shu-Yan Ji, Lan-Rui Cao, Song-Ying Zhang, Li Shen, Xiang-Hong Ou, Heng-Yu Fan
During mammalian oocyte growth, chromatin configuration transition from the nonsurrounded nucleolus (NSN) to surrounded nucleolus (SN) type plays a key role in the regulation of gene expression and acquisition of meiotic and developmental competence by the oocyte. Nonetheless, the mechanism underlying chromatin configuration maturation in oocytes is poorly understood. Here we show that nucleolar protein DCAF13 is an important component of the ribosomal RNA (rRNA)-processing complex and is essential for oocyte NSN-SN transition in mice...
October 3, 2018: Cell Death and Differentiation
Varnesh Tiku, Chun Kew, Parul Mehrotra, Raja Ganesan, Nirmal Robinson, Adam Antebi
Innate immunity is the first line of defense against infections. Pathways regulating innate responses can also modulate other processes, including stress resistance and longevity. Increasing evidence suggests a role for the nucleolus in regulating cellular processes implicated in health and disease. Here we show the highly conserved nucleolar protein, fibrillarin, is a vital factor regulating pathogen resistance. Fibrillarin knockdown enhances resistance in C. elegans against bacterial pathogens, higher levels of fibrillarin induce susceptibility to infection...
September 6, 2018: Nature Communications
Jin-Shu He, Priscilla Soo, Maurits Evers, Kate M Parsons, Nadine Hein, Katherine M Hannan, Ross D Hannan, Amee J George
The nucleolus is a dynamic subnuclear compartment that has a number of different functions, but its primary role is to coordinate the production and assembly of ribosomes. For well over 100 years, pathologists have used changes in nucleolar number and size to stage diseases such as cancer. New information about the nucleolus' broader role within the cell is leading to the development of drugs which directly target its structure as therapies for disease. Traditionally, it has been difficult to develop high-throughput image analysis pipelines to measure nucleolar changes due to the broad range of morphologies observed...
August 2018: Assay and Drug Development Technologies
Maaike Boonstra, Bart J A Mertens, Jaap A Bakker, Maarten K Ninaber, Nina Ajmone Marsan, Annette H M van der Helm-van Mil, Hans Ulrich Scherer, Tom W J Huizinga, Jeska K de Vries-Bouwstra
OBJECTIVES: To evaluate the additive value of autoantibodies in identifying systemic sclerosis (SSc) patients with high complication risk. METHODS: Patients entering the Combined Care In SSc cohort, Leiden University Medical Centre between April 2009 and May 2016 were included. Subgroups of patients were determined using hierarchical clustering, performed on Principal Component Analysis scores, 1) using baseline data of demographic and clinical variables only and 2) with additional use of antibody status...
July 2018: Clinical and Experimental Rheumatology
Sang-Cheol Bae, Young Ho Lee
Our purpose was to identify differentially expressed (DE) genes and biological processes associated with gene expression changes in systemic lupus erythematosus (SLE). We performed a meta-analysis using the INMEX program (integrative meta-analysis of expression data) on publicly available microarray Genetic Expression Omnibus (GEO) datasets of peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. We performed Gene Ontology (GO) enrichment analysis by using hypergeometric tests. In total, five comparisons (2 B cells, 2 CD4 T cells, and 1 myeloid cell) from two GEO datasets containing 51 cases and 46 controls were included in the meta-analysis...
July 30, 2018: Cellular and Molecular Biology
Maria Y Shubina, Yana R Musinova, Eugene V Sheval
Fibrillarin is an essential nucleolar protein that catalyzes the 2'-O-methylation of ribosomal RNAs. Recently, experimental data have begun to accumulate that suggest that fibrillarin can influence various cellular processes, development of pathological processes, and even aging. The exact mechanism by which fibrillarin can influence these processes has not been found, but some experimental data indicate that up- or downregulation of fibrillarin can modify the ribosome structure and, thus, causе an alteration in relative efficiency with which various mRNAs are translated...
August 6, 2018: Cell Biology International
Mahmoud B Maina, Laura J Bailey, Sherin Wagih, Luca Biasetti, Saskia J Pollack, James P Quinn, Julian R Thorpe, Aidan J Doherty, Louise C Serpell
Tau is known for its pathological role in neurodegenerative diseases, including Alzheimer's disease (AD) and other tauopathies. Tau is found in many subcellular compartments such as the cytosol and the nucleus. Although its normal role in microtubule binding is well established, its nuclear role is still unclear. Here, we reveal that tau localises to the nucleolus in undifferentiated and differentiated neuroblastoma cells (SHSY5Y), where it associates with TIP5, a key player in heterochromatin stability and ribosomal DNA (rDNA) transcriptional repression...
July 31, 2018: Acta Neuropathologica Communications
Ayantika Sen Gupta, Gaurav Joshi, Sumit Pawar, Kundan Sengupta
Eukaryotic cells have 2 to ​3 discrete nucleoli required for ribosome synthesis. Nucleoli are phase separated nuclear sub-organelles. Here we examined the role of nuclear Lamins and nucleolar factors in modulating the compartmentalization and dynamics of histone 2B (H2B-ECFP) in the nucleolus. Live imaging and Fluorescence Recovery After Photobleaching (FRAP) of labelled H2B, showed that the depletion of Lamin B1, Fibrillarin (FBL) or Nucleostemin (GNL3), enhances H2B-ECFP mobility in the nucleolus. Furthermore, Nucleolin knockdown significantly decreases H2B-ECFP compartmentalization in the nucleolus, while H2B-ECFP residence and mobility in the nucleolus was prolonged upon Nucleolin overexpression...
2018: Nucleus
Sara Rosińska, Anna Filipek
Calcyclin (S100A6) binding protein/Siah-1 interacting protein (CacyBP/SIP) is mainly a cytoplasmic protein; however, some literature data suggested its presence in the nucleus. In this work we examined more precisely the nuclear localization and function of CacyBP/SIP. By applying mass spectrometry, we have identified several nuclear proteins, among them is nucleophosmin (NPM1), that may interact with CacyBP/SIP. Subsequent assays revealed that CacyBP/SIP forms complexes with NPM1 in the cell and that the interaction between these two proteins is direct...
November 2018: Journal of Cellular Physiology
Luping Zheng, Jie He, Zuomei Ding, Chenlong Zhang, Ruoxue Meng
p2 of Rice stripe virus may promote virus systemic infection by interacting with the full length of fibrillarin from Nicotiana benthamiana (NbFib2) in the nucleolus and cajal body (CB). NbFib2 contains three functional domains. We used yeast two-hybrid, colocalization, and bimolecular fluorescence complementation (BiFC) assays to study the interactions between p2 and the three domains of NbFib2, namely, the N-terminal fragment containing a glycine and arginine-rich (GAR) domain, the central RNA-binding domain, and the C-terminal fragment containing an α -helical domain...
2018: Canadian Journal of Infectious Diseases & Medical Microbiology
Dingfeng Li, Juan Zhang, Ming Wang, Xiaohui Li, Huarui Gong, Huiping Tang, Lin Chen, Lili Wan, Qiang Liu
The ribosome is indispensable for precisely controlling the capacity of protein synthesis. However, how translational machinery is coordinated to meet the translational demands remains elusive. Here, we identify a nucleolar-specific lncRNA (LoNA), its 5' portion binds and sequesters nucleolin to suppress rRNA transcription, and its snoRNA like 3' end recruits and diminishes fibrillarin activity to reduce rRNA methylation. Activity-dependent decrease of LoNA leads to elevated rRNA and ribosome levels, an increased proportion of polysomes, mRNA polysome loading, and protein translation...
April 30, 2018: Nature Communications
Ingrida Smeringaiova, Stanislava Reinstein Merjava, Zbynek Stranak, Pavel Studeny, Jan Bednar, Katerina Jirsova
PURPOSE: To assess whether injured porcine endothelium of small and large corneoscleral disc differ in its reparative/regenerative capacity under various conditions of organ culture storage. MATERIAL AND METHODS: 166 paired porcine corneas were trephined to obtain tissues with diameter 12.0 mm and 17.5 mm (with area neighboring endothelial periphery). In tested discs, central endothelium was mechanically wounded. Density of live endothelial cells (LECD), percentage of dead cells (%DC), coefficient of variation and cell hexagonality were assessed in central and paracentral endothelium following 5- or 9-day incubation in medium with 2% or 10% fetal bovine serum...
July 2018: Current Eye Research
Roman J Szczesny, Katarzyna Kowalska, Kamila Klosowska-Kosicka, Aleksander Chlebowski, Ewelina P Owczarek, Zbigniew Warkocki, Tomasz M Kulinski, Dorota Adamska, Kamila Affek, Agata Jedroszkowiak, Anna V Kotrys, Rafal Tomecki, Pawel S Krawczyk, Lukasz S Borowski, Andrzej Dziembowski
Deciphering a function of a given protein requires investigating various biological aspects. Usually, the protein of interest is expressed with a fusion tag that aids or allows subsequent analyses. Additionally, downregulation or inactivation of the studied gene enables functional studies. Development of the CRISPR/Cas9 methodology opened many possibilities but in many cases it is restricted to non-essential genes. Recombinase-dependent gene integration methods, like the Flp-In system, are very good alternatives...
2018: PloS One
Stéphanie Bouffard, Emilie Dambroise, Alessandro Brombin, Sylvain Lempereur, Isabelle Hatin, Matthieu Simion, Raphaël Corre, Franck Bourrat, Jean-Stéphane Joly, Françoise Jamen
Fibrillarin (Fbl) is a highly conserved protein that plays an essential role in ribosome biogenesis and more particularly in the methylation of ribosomal RNAs and rDNA histones. In cellular models, FBL was shown to play an important role in tumorigenesis and stem cell differentiation. We used the zebrafish as an in vivo model to study Fbl function during embryonic development. We show here that the optic tectum and the eye are severely affected by Fbl depletion whereas ventral regions of the brain are less impacted...
May 1, 2018: Developmental Biology
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