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Article ; Online: Each Cellular Compartment Has a Characteristic Protein Reactive Cysteine Ratio Determining Its Sensitivity to Oxidation

Neves, Ricardo Pires das / Chagoyen, Mónica / Martinez-Lorente, Antonio / Iñiguez, Carlos / Calatrava, Ana / Calabuig, Juana / Iborra, Francisco J.

Antioxidants. 2023 June 14, v. 12, no. 6

2023

Abstract: Signaling and detoxification of Reactive Oxygen Species (ROS) are important patho-physiologcal processes. Despite this, we lack comprehensive information on individual cells and cellular structures and functions affected by ROS, which is essential to ... ...

Abstract	Signaling and detoxification of Reactive Oxygen Species (ROS) are important patho-physiologcal processes. Despite this, we lack comprehensive information on individual cells and cellular structures and functions affected by ROS, which is essential to build quantitative models of the effects of ROS. The thiol groups from cysteines (Cys) in proteins play a major role in redox defense, signaling, and protein function. In this study, we show that the proteins in each subcellular compartment contain a characteristic Cys amount. Using a fluorescent assay for -SH in thiolate form and amino groups in proteins, we show that the thiolate content correlates with ROS sensitivity and signaling properties of each compartment. The highest absolute thiolate concentration was found in the nucleolus, followed by the nucleoplasm and cytoplasm whereas protein thiolate groups per protein showed an inverse pattern. In the nucleoplasm, protein reactive thiols concentrated in SC35 speckles, SMN, and the IBODY that accumulated oxidized RNA. Our findings have important functional consequences, and explain differential sensitivity to ROS.
Keywords	RNA ; cell nucleolus ; cysteine ; cytoplasm ; fluorescence ; oxidation ; reactive oxygen species ; thiols
Language	English
Dates of publication	2023-0614
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12061274
Database	NAL-Catalogue (AGRICOLA)

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Article: Each Cellular Compartment Has a Characteristic Protein Reactive Cysteine Ratio Determining Its Sensitivity to Oxidation.

Neves, Ricardo Pires das / Chagoyen, Mónica / Martinez-Lorente, Antonio / Iñiguez, Carlos / Calatrava, Ana / Calabuig, Juana / Iborra, Francisco J

Antioxidants (Basel, Switzerland)

2023 Volume 12, Issue 6

Abstract	Signaling and detoxification of Reactive Oxygen Species (ROS) are important patho-physiologcal processes. Despite this, we lack comprehensive information on individual cells and cellular structures and functions affected by ROS, which is essential to build quantitative models of the effects of ROS. The thiol groups from cysteines (Cys) in proteins play a major role in redox defense, signaling, and protein function. In this study, we show that the proteins in each subcellular compartment contain a characteristic Cys amount. Using a fluorescent assay for -SH in thiolate form and amino groups in proteins, we show that the thiolate content correlates with ROS sensitivity and signaling properties of each compartment. The highest absolute thiolate concentration was found in the nucleolus, followed by the nucleoplasm and cytoplasm whereas protein thiolate groups per protein showed an inverse pattern. In the nucleoplasm, protein reactive thiols concentrated in SC35 speckles, SMN, and the IBODY that accumulated oxidized RNA. Our findings have important functional consequences, and explain differential sensitivity to ROS.
Language	English
Publishing date	2023-06-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox12061274
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Article ; Online: Chemotherapy induces cell plasticity; controlling plasticity increases therapeutic response.

Iborra, Francisco J / Martí, Cristina / Calabuig-Navarro, Virtu / Papadopoulos, Petros / Meseguer, Salvador / Iborra, Pedro M / García, Francisco / Martínez-Lorente, Antonio / Almazán, Fernando / Calabuig, Juana

Signal transduction and targeted therapy

2023 Volume 8, Issue 1, Page(s) 256

MeSH term(s)	Cell Plasticity ; Neuronal Plasticity/physiology
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-023-01500-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

Iborra, Francisco J

Theoretical biology & medical modelling

2007 Volume 4, Page(s) 15

Abstract: Background: The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute ... ...

Abstract	Background: The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. Results: The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin) scattered within domains rich in fast components (protein/RNA). Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. Conclusion: I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon.
MeSH term(s)	Cell Nucleus/chemistry ; Cell Nucleus/ultrastructure ; Chromatin/chemistry ; Colloids ; DNA/chemistry ; Elasticity ; Macromolecular Substances/chemistry ; Physical Phenomena ; Physics ; Proteins/chemistry ; Viscosity
Chemical Substances	Chromatin ; Colloids ; Macromolecular Substances ; Proteins ; DNA (9007-49-2)
Language	English
Publishing date	2007-04-12
Publishing country	England
Document type	Research Support, Non-U.S. Gov't
ZDB-ID	2156462-0
ISSN	1742-4682 ; 1742-4682
ISSN (online)	1742-4682
ISSN	1742-4682
DOI	10.1186/1742-4682-4-15
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mitochondria and the non-genetic origins of cell-to-cell variability: More is different.

Guantes, Raúl / Díaz-Colunga, Juan / Iborra, Francisco J

BioEssays : news and reviews in molecular, cellular and developmental biology

2016 Volume 38, Issue 1, Page(s) 64–76

Abstract: Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection, or cell fate choice. The ... ...

Abstract	Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection, or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells, most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Here, we discuss how differences in the mitochondrial content of each cell contribute to heterogeneity in gene products. Changes in the amount of mitochondria can also entail drastic alterations of a cell's gene expression program, which ultimately leads to phenotypic diversity. Also watch the Video Abstract.
MeSH term(s)	Alternative Splicing/genetics ; DNA, Mitochondrial/genetics ; Eukaryotic Cells ; Gene Expression Regulation/genetics ; Genetic Heterogeneity ; Humans ; Mitochondria/genetics ; Transcription, Genetic
Chemical Substances	DNA, Mitochondrial
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201500082
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Can visco-elastic phase separation, macromolecular crowding and colloidal physics explain nuclear organisation?

Iborra Francisco J

Theoretical Biology and Medical Modelling, Vol 4, Iss 1, p

2007 Volume 15

Abstract: Abstract Background The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to ... ...

Abstract	Abstract Background The cell nucleus is highly compartmentalized with well-defined domains, it is not well understood how this nuclear order is maintained. Many scientists are fascinated by the different set of structures observed in the nucleus to attribute functions to them. In order to distinguish functional compartments from non-functional aggregates, I believe is important to investigate the biophysical nature of nuclear organisation. Results The various nuclear compartments can be divided broadly as chromatin or protein and/or RNA based, and they have very different dynamic properties. The chromatin compartment displays a slow, constrained diffusional motion. On the other hand, the protein/RNA compartment is very dynamic. Physical systems with dynamical asymmetry go to viscoelastic phase separation. This phase separation phenomenon leads to the formation of a long-lived interaction network of slow components (chromatin) scattered within domains rich in fast components (protein/RNA). Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml. This high concentration of macromolecules produces volume exclusion effects that enhance attractive interactions between macromolecules, known as macromolecular crowding, which favours the formation of compartments. In this paper I hypothesise that nuclear compartmentalization can be explained by viscoelastic phase separation of the dynamically different nuclear components, in combination with macromolecular crowding and the properties of colloidal particles. Conclusion I demonstrate that nuclear structure can satisfy the predictions of this hypothesis. I discuss the functional implications of this phenomenon.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2007-04-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Photoluminescence Activation of Organic Dyes via Optically Trapped Quantum Dots.

Rodríguez-Rodríguez, Héctor / Acebrón, María / Iborra, Francisco J / Arias-Gonzalez, J Ricardo / Juárez, Beatriz H

ACS nano

2019 Volume 13, Issue 6, Page(s) 7223–7230

Abstract: Laser tweezers afford quantum dot (QD) manipulation for use as localized emitters. Here, we demonstrate fluorescence by radiative energy transfer from optically trapped colloidal QDs (donors) to fluorescent dyes (acceptors). To this end, we synthesized ... ...

Abstract	Laser tweezers afford quantum dot (QD) manipulation for use as localized emitters. Here, we demonstrate fluorescence by radiative energy transfer from optically trapped colloidal QDs (donors) to fluorescent dyes (acceptors). To this end, we synthesized silica-coated QDs of different compositions and triggered their luminescence by simultaneous trapping and two-photon excitation in a microfluidic chamber filled with dyes. This strategy produces a near-field light source with great spatial maneuverability, which can be exploited to scan nanostructures. In this regard, we demonstrate induced photoluminescence of dye-labeled cells via optically trapped silica-coated colloidal QDs placed at their vicinity. Allocating nanoscale donors at controlled distances from a cell is an attractive concept in fluorescence microscopy because it dramatically reduces the number of excited dyes, which improves resolution by preventing interferences from the whole sample, while prolonging dye luminescence lifetime due to the lower power absorbed from the QDs.
Language	English
Publishing date	2019-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.9b02835
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: SARS-CoV-2-encoded small RNAs are able to repress the host expression of SERINC5 to facilitate viral replication.

Meseguer, Salvador / Rubio, Mari-Paz / Lainez, Begoña / Pérez-Benavente, Beatriz / Pérez-Moraga, Raúl / Romera-Giner, Sergio / García-García, Francisco / Martinez-Macias, Olalla / Cremades, Antonio / Iborra, Francisco J / Candelas-Rivera, Oscar / Almazan, Fernando / Esplugues, Enric

Frontiers in microbiology

2023 Volume 14, Page(s) 1066493

Abstract: Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled ... ...

Abstract	Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3'-untranslated region (3'-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3'UTR of SERINC5 mRNA, reducing SERINC5 expression
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2023.1066493
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The path that RNA takes from the nucleus to the cytoplasm: a trip with some surprises.

Iborra, Francisco J

Histochemistry and cell biology

2002 Volume 118, Issue 2, Page(s) 95–103

Abstract: It is now clear that nuclear context is playing an essential role in gene expression. For this reason we have developed methods to study gene expression in situ. Transcription takes place in discrete foci in the nucleoplasm of mammalian cells. These ... ...

Abstract	It is now clear that nuclear context is playing an essential role in gene expression. For this reason we have developed methods to study gene expression in situ. Transcription takes place in discrete foci in the nucleoplasm of mammalian cells. These sites concentrate several RNA polymerases II and factors involved in the production of mRNA. Moreover, these sites also contain the active machinery to carry out protein synthesis. Once the mRNA leaves the transcription site, it interacts with the nuclear pore complex and the mRNA is exported using the filaments of the nuclear pore complex in to the middle part of the nuclear pore complex and finally is released in the cytoplasm.
MeSH term(s)	Active Transport, Cell Nucleus/physiology ; Animals ; Cell Nucleus ; Gene Expression Regulation ; Humans ; Nuclear Pore/physiology ; RNA Polymerase II/analysis ; RNA Polymerase II/metabolism ; RNA, Messenger/metabolism ; Transcription, Genetic
Chemical Substances	RNA, Messenger ; RNA Polymerase II (EC 2.7.7.-)
Language	English
Publishing date	2002-07-04
Publishing country	Germany
Document type	Lecture ; Research Support, Non-U.S. Gov't
ZDB-ID	1222930-1
ISSN	1432-119X ; 0948-6143 ; 0301-5564
ISSN (online)	1432-119X
ISSN	0948-6143 ; 0301-5564
DOI	10.1007/s00418-002-0441-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A natural polymorphism in Zika virus NS2A protein responsible of virulence in mice.

Ávila-Pérez, Gines / Nogales, Aitor / Park, Jun-Gyu / Márquez-Jurado, Silvia / Iborra, Francisco J / Almazan, Fernando / Martínez-Sobrido, Luis

Scientific reports

2019 Volume 9, Issue 1, Page(s) 19968

Abstract: Zika virus (ZIKV) infection is currently one of the major concerns in human public health due to its association with neurological disorders. Intensive effort has been implemented for the treatment of ZIKV, however there are not currently approved ... ...

Abstract	Zika virus (ZIKV) infection is currently one of the major concerns in human public health due to its association with neurological disorders. Intensive effort has been implemented for the treatment of ZIKV, however there are not currently approved vaccines or antivirals available to combat ZIKV infection. In this sense, the identification of virulence factors associated with changes in ZIKV virulence could help to develop safe and effective countermeasures to treat ZIKV or to prevent future outbreaks. Here, we have compared the virulence of two related ZIKV strains from the recent outbreak in Brazil (2015), Rio Grande do Norte Natal (RGN) and Paraiba. In spite of both viruses being identified in the same period of time and region, significant differences in virulence and replication were observed using a validated mouse model of ZIKV infection. While ZIKV-RGN has a 50% mouse lethal dose (MLD
MeSH term(s)	Amino Acid Substitution ; Animals ; Apoptosis ; Cell Line ; Disease Models, Animal ; Female ; Genome, Viral ; Genomics/methods ; Host-Pathogen Interactions ; Immunity, Innate ; Mice ; Polymorphism, Genetic ; Viral Nonstructural Proteins/genetics ; Virulence/genetics ; Virus Replication ; Zika Virus/physiology ; Zika Virus Infection/immunology ; Zika Virus Infection/virology
Chemical Substances	Viral Nonstructural Proteins
Keywords	covid19
Language	English
Publishing date	2019-12-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-56291-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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