scholarly journals Splice sites obey the power-law during splicing in leukemia cells

2021 ◽  
Author(s):  
Vasily V Grinev ◽  
Natalia Siomava ◽  
Laurent Vallar ◽  
Petr V Nazarov
Keyword(s):  
Alternative Splicing ◽  
Power Law ◽  
Living Cells ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Splice Sites ◽  
Essential Characteristic ◽  
Exon Junction ◽  
Traditional Classification ◽  
First Time

Alternative splicing is an essential characteristic of living cells that usually infers a various exon-exon junction governed by different splice sites. The traditional classification based on the mode of use designates splice site to one of the two groups, constitutive or alternative. Here, we considered another criterion and reorganized splice sites into "unisplice" and "multisplice" groups according to the number of undertaken splicing events. This approach provided us with a new insight in the organization and functionality of leukemia cells. We determined features associated with uni- and multisplice sites and found that combinatorics of these sites follows strict rules of the power-law in the t(8;21)-positive leukemia cells. We also found that system splicing characteristics of the transcriptome of leukemia cells remained persistent after drastic changes in the transcript composition caused by knockdown of the RUNX1-RUNX1T1 oncogene. In this work, we show for the first time that leukemia cells possess a sub-set of unisplice sites with a hidden multisplice potential. These findings reveal a new side in organization and functioning of the leukemic cells and open up new perspectives in the study of the t(8;21)-positive leukemia.

scholarly journals Alternative Splicing of Transcripts from crtI and crtYB Genes of Xanthophyllomyces dendrorhous

2003 ◽  
Vol 69 (8) ◽  
pp. 4676-4682 ◽  
Author(s):  
P. Lodato ◽  
J. Alcaino ◽  
S. Barahona ◽  
P. Retamales ◽  
V. Cifuentes
Keyword(s):  
Alternative Splicing ◽  
Environmental Conditions ◽  
Phytoene Desaturase ◽  
Xanthophyllomyces Dendrorhous ◽  
Splice Sites ◽  
Alternative Transcripts ◽  
First Intron ◽  
Mature Mrna ◽  
Lycopene Cyclase ◽  
First Time

ABSTRACT Xanthophyllomyces dendrorhous is one of the relevant sources of the carotenoid astaxanthin. In this paper, we describe for the first time cloning of unexpected cDNAs obtained from the crtI and crtYB genes of X. dendrorhous strain UCD 67-385. The cDNA of the crtI gene conserves 80 bp of the first intron, while the cDNA of the crtYB gene conserves 55 bp of the first intron and lacks 111 bp of the second exon. The crtI and crtYB RNAs could be spliced in alternative splice sites, which produced alternative transcripts which could not be translated to active CRTI and CRTYB proteins since they had numerous stop codons in their sequences. The ratio of mature mRNA to alternative mRNA for the crtI gene decreased as a function of the age of the culture, while the cellular content of carotenoids increased. It is possible that splicing to mature or alternative transcripts could regulate the cellular concentrations of phytoene desaturase and phytoene synthase-lycopene cyclase proteins, depending on the physiological or environmental conditions.

Carbon dots derived from Fusobacterium nucleatum for intracellular determination of Fe3+ and bioimaging both in vitro and in vivo

2021 ◽  
Author(s):  
Lijuan Liu ◽  
Shengting Zhang ◽  
Xiaodan Zheng ◽  
Hongmei Li ◽  
Qi Chen ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Fusobacterium Nucleatum ◽  
Living Cells ◽  
First Time ◽  
Fluorescent Carbon Dots ◽  
Fluorescent Carbon

Fusobacterium nucleatum has been employed for the first time to synthesize fluorescent carbon dots which could be applied for the determination of Fe3+ ions in living cells and bioimaging in vitro and in vivo with excellent biocompatibility.

Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA

1993 ◽  
Vol 13 (9) ◽  
pp. 5461-5468
Author(s):  
E Gilbert ◽  
F Del Gatto ◽  
P Champion-Arnaud ◽  
M C Gesnel ◽  
R Breathnach
Keyword(s):  
Alternative Splicing ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Splice Sites ◽  
Polypyrimidine Tract ◽  
Profound Influence ◽  
In Cells

The fibroblast growth factor receptor 2 gene pre-mRNA can be spliced by using either the K-SAM exon or the BEK exon. The exon chosen has a profound influence on the ligand-binding specificity of the receptor obtained. Cells make a choice between the two alternative exons by controlling use of both exons. Using fibroblast growth factor receptor 2 minigenes, we have shown that in cells normally using the K-SAM exon, the BEK exon is not used efficiently even in the absence of the K-SAM exon. This is because these cells apparently express a titratable repressor of BEK exon use. In cells normally using the BEK exon, the K-SAM exon is not used efficiently even in the absence of a functional BEK exon. Three purines in the K-SAM polypyrimidine tract are at least in part responsible for this, as their mutation to pyrimidines leads to efficient use of the K-SAM exon, while mutating the BEK polypyrimidine tract to include these purines stops BEK exon use.

scholarly journals Dynamic nanoscale morphology of the ER surveyed by STED microscopy

2018 ◽  
Vol 218 (1) ◽  
pp. 83-96 ◽  
Author(s):  
Lena K. Schroeder ◽  
Andrew E.S. Barentine ◽  
Holly Merta ◽  
Sarah Schweighofer ◽  
Yongdeng Zhang ◽  
...  
Keyword(s):  
Living Cells ◽  
Stimulated Emission ◽  
Membrane Structures ◽  
Spatiotemporal Resolution ◽  
Sted Microscopy ◽  
Superresolution Microscopy ◽  
Structure And Dynamics ◽  
First Time ◽  
Nanoscale Dynamics ◽  
Conventional Light Microscopy

The endoplasmic reticulum (ER) is composed of interconnected membrane sheets and tubules. Superresolution microscopy recently revealed densely packed, rapidly moving ER tubules mistaken for sheets by conventional light microscopy, highlighting the importance of revisiting classical views of ER structure with high spatiotemporal resolution in living cells. In this study, we use live-cell stimulated emission depletion (STED) microscopy to survey the architecture of the ER at 50-nm resolution. We determine the nanoscale dimensions of ER tubules and sheets for the first time in living cells. We demonstrate that ER sheets contain highly dynamic, subdiffraction-sized holes, which we call nanoholes, that coexist with uniform sheet regions. Reticulon family members localize to curved edges of holes within sheets and are required for their formation. The luminal tether Climp63 and microtubule cytoskeleton modulate their nanoscale dynamics and organization. Thus, by providing the first quantitative analysis of ER membrane structure and dynamics at the nanoscale, our work reveals that the ER in living cells is not limited to uniform sheets and tubules; instead, we suggest the ER contains a continuum of membrane structures that includes dynamic nanoholes in sheets as well as clustered tubules.

scholarly journals Amount of RNA secondary structure required to induce an alternative splice.

1987 ◽  
Vol 7 (9) ◽  
pp. 3194-3198 ◽  
Author(s):  
D Solnick ◽  
S I Lee
Keyword(s):  
Alternative Splicing ◽  
Secondary Structure ◽  
Alternative Splice ◽  
Rna Secondary Structure ◽  
Secondary Structures ◽  
Splice Sites ◽  
Perfect Complementarity ◽  
Set Up

We set up an alternative splicing system in vitro in which the relative amounts of two spliced RNAs, one containing and the other lacking a particular exon, were directly proportional to the length of an inverted repeat inserted into the flanking introns. We then used the system to measure the effect of intramolecular complementarity on alternative splicing in vivo. We found that an alternative splice was induced in vivo only when the introns contained more than approximately 50 nucleotides of perfect complementarity, that is, only when the secondary structure was much more stable than most if not all possible secondary structures in natural mRNA precursors. We showed further that intron insertions containing long complements to splice sites and a branch point inhibited splicing in vitro but not in vivo. These results raise the possibility that in cells most pre-mRNA secondary structures either are not maintained long enough to influence splicing choices, or never form at all.

scholarly journals Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1951-1956
Author(s):  
ED Ball ◽  
J McDermott ◽  
JD Griffin ◽  
FR Davey ◽  
R Davis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Acute Leukemia ◽  
Cell Sorting ◽  
Lymphoblastic Leukemia ◽  
Mononuclear Phagocytes ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Normal Bone Marrow ◽  
Normal Bone

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.

scholarly journals Cisplatin-induced apoptotic endonuclease EndoG inhibits telomerase activity and causes malignant transformation of human CD4+ T lymphocytes

2017 ◽  
Vol 63 (1) ◽  
pp. 13-26 ◽  
Author(s):  
D.D. Zhdanov ◽  
D.A. Vasina ◽  
E.V. Orlova ◽  
V.S. Orlova ◽  
V.S. Pokrovsky ◽  
...  
Keyword(s):  
T Cells ◽  
Alternative Splicing ◽  
Malignant Transformation ◽  
Cd4 T Cells ◽  
Replicative Senescence ◽  
Telomerase Activity ◽  
Full Length ◽  
Leukemic Cells ◽  
Proliferative Potential ◽  
Human Telomerase Reverse Transcriptase

Alternative splicing of telomerase catalytic subunit hTERT pre-mRNA (human Telomerase Reverse Transcriptase) regulates telomerase activity. Increased expression of non-active splice variant hTERT results in inhibition of telomerase. Apoptotic endonuclease EndoG is known to participate in hTERT alternative splicing. Expression of EndoG can be induced in response to DNA damages. The aim of this study was to determine the ability of a DNA-damaging compound, cisplatin, to induce EndoG and its influence on alternative splicing of hTERT and telomerase activity in human CD4+ Т lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated the expression of active full-length hTERT variant and upregulated its non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. Few cells survived and underwent malignant transformation. Transformed cells have increased telomerase activity and proliferative potential compare to initial CD4+ T cells. These cells have phenotype of T lymphoblastic leukemic cells and are able to form tumors and cause death in experimental mice.

scholarly journals Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

2012 ◽  
Vol 2 (4) ◽  
pp. 72 ◽  
Author(s):  
Diana Bayer ◽  
Jonathon Jansen ◽  
Lisa A. Beltz
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Peripheral Blood Mononuclear ◽  
Normal Cells

Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl)-diphenyltetrazolium bromide) assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes. Conclusions: The three tea extracts studied altered leukemic T lymphocyte functions, decreasing cell viability, growth, and production of a major cell growth factor and the H2O2 generated by solutions of extracts may be partially responsible. Normal cells were affected to a far lesser degree by tea extracts and are also more resistant to killing by H2O2 than leukemic cells. This study has implications for using tea extracts for chemotherapeutic and immunomodulatory purposes.Key Words: Tea extracts, interleukin-2, hydrogen peroxide, leukemia, T lymphocytes

scholarly journals Detection of the Geminga pulsar with MAGIC hints at a power-law tail emission beyond 15 GeV

2020 ◽  
Vol 643 ◽  
pp. L14
Author(s):  
◽  
V. A. Acciari ◽  
S. Ansoldi ◽  
L. A. Antonelli ◽  
A. Arbet Engels ◽  
...  
Keyword(s):  
Energy Range ◽  
Power Law ◽  
Gamma Ray ◽  
Low Energy ◽  
Significance Level ◽  
Inverse Compton Scattering ◽  
Curvature Radiation ◽  
Sensitivity Range ◽  
Inverse Compton ◽  
First Time

We report the detection of pulsed gamma-ray emission from the Geminga pulsar (PSR J0633+1746) between 15 GeV and 75 GeV. This is the first time a middle-aged pulsar has been detected up to these energies. Observations were carried out with the MAGIC telescopes between 2017 and 2019 using the low-energy threshold Sum-Trigger-II system. After quality selection cuts, ∼80 h of observational data were used for this analysis. To compare with the emission at lower energies below the sensitivity range of MAGIC, 11 years of Fermi-LAT data above 100 MeV were also analysed. From the two pulses per rotation seen by Fermi-LAT, only the second one, P2, is detected in the MAGIC energy range, with a significance of 6.3σ. The spectrum measured by MAGIC is well-represented by a simple power law of spectral index Γ = 5.62 ± 0.54, which smoothly extends the Fermi-LAT spectrum. A joint fit to MAGIC and Fermi-LAT data rules out the existence of a sub-exponential cut-off in the combined energy range at the 3.6σ significance level. The power-law tail emission detected by MAGIC is interpreted as the transition from curvature radiation to Inverse Compton Scattering of particles accelerated in the northern outer gap.

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