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https://www.readbyqxmd.com/read/29769721/spatiotemporal-regulation-of-liquid-like-condensates-in-epigenetic-inheritance
#1
Gang Wan, Brandon D Fields, George Spracklin, Aditi Shukla, Carolyn M Phillips, Scott Kennedy
Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29768216/the-rna-exosome-adaptor-zfc3h1-functionally-competes-with-nuclear-export-activity-to-retain-target-transcripts
#2
Toomas Silla, Evdoxia Karadoulama, Dawid Mąkosa, Michal Lubas, Torben Heick Jensen
Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+ ) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29738469/the-role-of-scarnas-in-adjusting-alternative-mrna-splicing-in-heart-development
#3
REVIEW
Chloe Nagasawa, Allison Ogren, Nataliya Kibiryeva, Jennifer Marshall, James E O'Brien, Naoya Kenmochi, Douglas C Bittel
Congenital heart disease (CHD) is a leading cause of death in children <1 year of age. Despite intense effort in the last 10 years, most CHDs (~70%) still have an unknown etiology. Conotruncal based defects, such as Tetralogy of Fallot (TOF), a common complex of devastating heart defects, typically requires surgical intervention in the first year of life. We reported that the noncoding transcriptome in myocardial tissue from children with TOF is characterized by significant variation in levels of expression of noncoding RNAs, and more specifically, a significant reduction in 12 small cajal body-associated RNAs (scaRNAs) in the right ventricle...
May 8, 2018: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29736196/identification-of-functional-domain-s-of-fibrillarin-interacted-with-p2-of-rice-stripe-virus
#4
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
https://www.readbyqxmd.com/read/29695869/cryo-em-structure-of-substrate-bound-human-telomerase-holoenzyme
#5
Thi Hoang Duong Nguyen, Jane Tam, Robert A Wu, Basil J Greber, Daniel Toso, Eva Nogales, Kathleen Collins
The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, and ageing, but progress towards clinical manipulation of telomerase has been hampered by the lack of structural data. Here we present the cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme at subnanometre resolution, showing two flexibly RNA-tethered lobes: the catalytic core with telomerase reverse transcriptase (TERT) and conserved motifs of telomerase RNA (hTR), and an H/ACA ribonucleoprotein (RNP)...
April 25, 2018: Nature
https://www.readbyqxmd.com/read/29669292/parn-and-toe1-constitute-a-3-end-maturation-module-for-nuclear-non-coding-rnas
#6
Ahyeon Son, Jong-Eun Park, V Narry Kim
Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29667248/establishment-of-a-radiotelemetric-recording-technique-in-mice-to-investigate-gastric-slow-waves-modulatory-role-of-putative-neurotransmitter-systems
#7
Huichuan Wang, Zengbing Lu, Yuen Hang Liu, Yayi Sun, Longlong Tu, Man P Ngan, Chi-Kong Yeung, John A Rudd
NEW FINDINGS: What is the central question of this study? Gastric slow waves originating from interstitial cells of Cajal-smooth muscle syncytium are usually studied in culture or in tissue segments, but no studies have made recording of slow waves from conscious freely moving mice. Can radiotelemetry be used to record slow waves, and do they respond predictably to drug treatment? What is the main finding and its importance? Radiotelemetry may be used to record slow waves from conscious freely moving mice permitting an examination of drug action in vivo, which is critical to drug discovery projects characterizing drugs and metabolites on gastrointestinal function...
April 18, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29626542/no-gc-in-cells-off-the-beaten-track
#8
REVIEW
Andreas Friebe, Barbara Voußen, Dieter Groneberg
Nitric oxide-sensitive guanylyl cyclase (NO-GC) has been shown to regulate a plethora of different functions in the body. These include, among many others, the fine-tuning of vascular tone, platelet reactivity and gastrointestinal motility. Evidence for the participation of NO-GC in these functions has been obtained from various species including humans, rodents, as well as insects. Clearly, individual cell types that express NO-GC contribute differentially to organ-specific NO/cGMP signaling in the body. Hence, identification of NO-GC-expressing cells and their individual involvement in NO/cGMP signaling constituted the focus of many studies over the last 40 years...
April 4, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29516630/wdr79-mediates-the-proliferation-of-non-small-cell-lung-cancer-cells-by-regulating-the-stability-of-uhrf1
#9
Jieying Chen, Xunan Sheng, Hongchang Ma, Zhengshan Tang, Chao Yang, Lanqin Cao, Yang Sun, Tanggang Deng, Peifu Feng, Bin Hu, Dong Wei, Jing Liu, Wei Xiong, Mao Ye
WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family characterized by the presence of a series of WD-repeat domains and is a scaffold protein that participates in telomerase assembly, Cajal body formation and DNA double strand break repair. Although previous studies have revealed that WDR79 is frequently overexpressed in non-small cell lung cancer (NSCLC) and promotes the proliferation of NSCLC cells, the underlying mechanism responsible for WDR79-mediated NSCLC proliferation is not fully understood...
May 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29479362/the-multiple-functions-of-the-nucleolus-in-plant-development-disease-and-stress-responses
#10
REVIEW
Natalia O Kalinina, Svetlana Makarova, Antonida Makhotenko, Andrew J Love, Michael Taliansky
The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29473743/dynamics-and-function-of-nuclear-bodies-during-embryogenesis
#11
Dahyana Arias Escayola, Karla M Neugebauer
Nuclear bodies are RNA-rich membraneless organelles in the cell nucleus that concentrate specific sets of nuclear proteins and RNA-protein complexes. Nuclear bodies such as the nucleolus, Cajal body (CB), and the histone locus body (HLB) concentrate factors required for nuclear steps of RNA processing. Formation of these nuclear bodies occurs on genomic loci and is frequently associated with active sites of transcription. Whether nuclear body formation is dependent on a particular gene element, an active process such as transcription, or the nascent RNA present at gene loci is a topic of debate...
May 1, 2018: Biochemistry
https://www.readbyqxmd.com/read/29471365/integrator-subunit-4-is-a-symplekin-like-scaffold-that-associates-with-ints9-11-to-form-the-integrator-cleavage-module
#12
Todd R Albrecht, Sergey P Shevtsov, Yixuan Wu, Lauren G Mascibroda, Natoya J Peart, Kai-Lieh Huang, Iain A Sawyer, Liang Tong, Miroslav Dundr, Eric J Wagner
Integrator (INT) is a transcriptional regulatory complex associated with RNA polymerase II that is required for the 3'-end processing of both UsnRNAs and enhancer RNAs. Integrator subunits 9 (INTS9) and INTS11 constitute the catalytic core of INT and are paralogues of the cleavage and polyadenylation specificity factors CPSF100 and CPSF73. While CPSF73/100 are known to associate with a third protein called Symplekin, there is no paralog of Symplekin within INT raising the question of how INTS9/11 associate with the other INT subunits...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29415178/the-sm-core-mediates-the-retention-of-partially-assembled-spliceosomal-snrnps-in-cajal-bodies-until-their-full-maturation
#13
Adriana Roithová, Klára Klimešová, Josef Pánek, Cindy L Will, Reinhard Lührmann, David Stanek, Cyrille Girard
Cajal bodies (CBs) are nuclear non-membrane bound organelles where small nuclear ribonucleoprotein particles (snRNPs) undergo their final maturation and quality control before they are released to the nucleoplasm. However, the molecular mechanism how immature snRNPs are targeted and retained in CBs has yet to be described. Here, we microinjected and expressed various snRNA deletion mutants as well as chimeric 7SK, Alu or bacterial SRP non-coding RNAs and provide evidence that Sm and SMN binding sites are necessary and sufficient for CB localization of snRNAs...
February 5, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29391529/small-molecule-flunarizine-increases-smn-protein-in-nuclear-cajal-bodies-and-motor-function-in-a-mouse-model-of-spinal-muscular-atrophy
#14
Delphine Sapaly, Matthieu Dos Santos, Perrine Delers, Olivier Biondi, Gwendoline Quérol, Léo Houdebine, Kevinee Khoobarry, François Girardet, Philippe Burlet, Anne-Sophie Armand, Christophe Chanoine, Jean-François Bureau, Frédéric Charbonnier, Suzie Lefebvre
The hereditary neurodegenerative disorder spinal muscular atrophy (SMA) is characterized by the loss of spinal cord motor neurons and skeletal muscle atrophy. SMA is caused by mutations of the survival motor neuron (SMN) gene leading to a decrease in SMN protein levels. The SMN deficiency alters nuclear body formation and whether it can contribute to the disease remains unclear. Here we screen a series of small-molecules on SMA patient fibroblasts and identify flunarizine that accumulates SMN into Cajal bodies, the nuclear bodies important for the spliceosomal small nuclear RNA (snRNA)-ribonucleoprotein biogenesis...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29371219/-gemin4-is-an-essential-gene-in-mice-and-its-overexpression-in-human-cells-causes-relocalization-of-the-smn-complex-to-the-nucleoplasm
#15
Ingo D Meier, Michael P Walker, A Gregory Matera
Gemin4 is a member of the Survival Motor Neuron (SMN) protein complex, which is responsible for the assembly and maturation of Sm-class small nuclear ribonucleoproteins (snRNPs). In metazoa, Sm snRNPs are assembled in the cytoplasm and subsequently imported into the nucleus. We previously showed that the SMN complex is required for snRNP import in vitro , although it remains unclear which specific components direct this process. Here, we report that Gemin4 overexpression drives SMN and the other Gemin proteins from the cytoplasm into the nucleus...
February 1, 2018: Biology Open
https://www.readbyqxmd.com/read/29193736/development-of-interstitial-cells-of-cajal-in-the-human-digestive-tract-as-the-result-of-reciprocal-induction-of-mesenchymal-and-neural-crest-cells
#16
REVIEW
Goran Radenkovic, Dina Radenkovic, Aleksandra Velickov
Neural crest cells (NCC) can migrate into different parts of the body and express their strong inductive potential. In addition, they are multipotent and are able to differentiate into various cell types with diverse functions. In the primitive gut, NCC induce differentiation of muscular structures and interstitial cells of Cajal (ICC), and they themselves differentiate into the elements of the enteric nervous system (ENS), neurons and glial cells. ICC develop by way of mesenchymal cell differentiation in the outer parts of the primitive gut wall around the myenteric plexus (MP) ganglia, with the exception of colon, where they appear simultaneously also at the submucosal border of the circular muscular layer around the submucosal plexus (SMP) ganglia...
February 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29163603/novel-ribonuclease-activity-differs-between-fibrillarins-from-arabidopsis-thaliana
#17
Ulises Rodriguez-Corona, Alejandro Pereira-Santana, Margarita Sobol, Luis C Rodriguez-Zapata, Pavel Hozak, Enrique Castano
Fibrillarin is one of the most important nucleolar proteins that have been shown as essential for life. Fibrillarin localizes primarily at the periphery between fibrillar center and dense fibrillar component as well as in Cajal bodies. In most plants there are at least two different genes for fibrillarin. In Arabidopsis thaliana both genes show high level of expression in transcriptionally active cells. Here, we focus on two important differences between A. thaliana fibrillarins. First and most relevant is the enzymatic activity by AtFib2...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28879433/cbp-mediated-smn-acetylation-modulates-cajal-body-biogenesis-and-the-cytoplasmic-targeting-of-smn
#18
Vanesa Lafarga, Olga Tapia, Sahil Sharma, Rocio Bengoechea, Georg Stoecklin, Miguel Lafarga, Maria T Berciano
The survival of motor neuron (SMN) protein plays an essential role in the biogenesis of spliceosomal snRNPs and the molecular assembly of Cajal bodies (CBs). Deletion of or mutations in the SMN1 gene cause spinal muscular atrophy (SMA) with degeneration and loss of motor neurons. Reduced SMN levels in SMA lead to deficient snRNP biogenesis with consequent splicing pathology. Here, we demonstrate that SMN is a novel and specific target of the acetyltransferase CBP (CREB-binding protein). Furthermore, we identify lysine (K) 119 as the main acetylation site in SMN...
February 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28878014/identification-of-a-35s-u4-u6-u5-tri-small-nuclear-ribonucleoprotein-tri-snrnp-complex-intermediate-in-spliceosome-assembly
#19
Zhe Chen, Bin Gui, Yu Zhang, Guojia Xie, Wanjin Li, Shumeng Liu, Bosen Xu, Chongyang Wu, Lin He, Jianguo Yang, Xia Yi, Xiaohan Yang, Luyang Sun, Jing Liang, Yongfeng Shang
The de novo assembly and post-splicing reassembly of the U4/U6.U5 tri-snRNP remain to be investigated. We report here that ZIP, a protein containing a CCCH-type zinc finger and a G-patch domain, as characterized by us previously, regulates pre-mRNA splicing independent of RNA binding. We found that ZIP physically associates with the U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP). Remarkably, the ZIP-containing tri-snRNP, which has a sedimentation coefficient of ∼35S, is a tri-snRNP that has not been described previously...
November 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28869095/biology-and-clinical-relevance-of-noncoding-sno-scarnas
#20
REVIEW
Thuy Cao, Sheeja Rajasingh, Saheli Samanta, Buddhadeb Dawn, Douglas C Bittel, Johnson Rajasingh
Small nucleolar RNAs (snoRNAs) are a group of noncoding RNAs that perform various biological functions, including biochemical modifications of other RNAs, precursors of miRNA, splicing, and telomerase activity. The small Cajal body-associated RNAs (scaRNAs) are a subset of the snoRNA family and collect in the Cajal body where they perform their canonical function to biochemically modify spliceosomal RNAs prior to maturation. Failure of sno/scaRNAs have been implicated in pathology such as congenital heart anomalies, neuromuscular disorders, and various malignancies...
February 2018: Trends in Cardiovascular Medicine
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