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  1. Article ; Online: Evolutionary divergence of

    Much, Christian / Smallegan, Michael J / Hwang, Taeyoung / Hanson, Skylar D / Dumbović, Gabrijela / Rinn, John L

    RNA (New York, N.Y.)

    2022  Volume 28, Issue 6, Page(s) 842–853

    Abstract: Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics and potential functions of lncRNAs with shared synteny remains unclear. Here we show that ...

    Abstract Long noncoding RNAs (lncRNAs) are rapidly evolving and thus typically poorly conserved in their sequences. How these sequence differences affect the characteristics and potential functions of lncRNAs with shared synteny remains unclear. Here we show that the syntenically conserved lncRNA
    MeSH term(s) Animals ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Mice ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism
    Chemical Substances RNA, Long Noncoding
    Language English
    Publishing date 2022-03-18
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1241540-6
    ISSN 1469-9001 ; 1355-8382
    ISSN (online) 1469-9001
    ISSN 1355-8382
    DOI 10.1261/rna.079070.121
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  2. Article ; Online: VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells.

    Rosales-Alvarez, Reyna Edith / Rettkowski, Jasmin / Herman, Josip Stefan / Dumbović, Gabrijela / Cabezas-Wallscheid, Nina / Grün, Dominic

    Genome biology

    2023  Volume 24, Issue 1, Page(s) 148

    Abstract: Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the ... ...

    Abstract Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.
    MeSH term(s) Mice ; Animals ; Hematopoietic Stem Cells ; Cell Differentiation/genetics ; Aging/genetics ; Gene Expression
    Language English
    Publishing date 2023-06-23
    Publishing country England
    Document type Journal Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-023-02974-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo.

    Carter, Thomas A / Singh, Manvendra / Dumbović, Gabrijela / Chobirko, Jason D / Rinn, John L / Feschotte, Cédric

    eLife

    2022  Volume 11

    Abstract: The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal ... ...

    Abstract The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH elements achieve such transcriptional specificity remains poorly understood. To uncover the sequence features underlying HERVH transcriptional activity, we performed a phyloregulatory analysis of the long terminal repeats (LTR7) of the HERVH family, which harbor its promoter, using a wealth of regulatory genomics data. We found that the family includes at least eight previously unrecognized subfamilies that have been active at different timepoints in primate evolution and display distinct expression patterns during human embryonic development. Notably, nearly all HERVH elements transcribed in ESCs belong to one of the youngest subfamilies we dubbed LTR7up. LTR7 sequence evolution was driven by a mixture of mutational processes, including point mutations, duplications, and multiple recombination events between subfamilies, that led to transcription factor binding motif modules characteristic of each subfamily. Using a reporter assay, we show that one such motif, a predicted SOX2/3 binding site unique to LTR7up, is essential for robust promoter activity in induced pluripotent stem cells. Together these findings illuminate the mechanisms by which HERVH diversified its expression pattern during evolution to colonize distinct cellular niches within the human embryo.
    MeSH term(s) Animals ; Endogenous Retroviruses/genetics ; Genomics ; Humans ; Pluripotent Stem Cells ; Primates/genetics ; Terminal Repeat Sequences/genetics
    Language English
    Publishing date 2022-02-18
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.76257
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  4. Article ; Online: VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells

    Reyna Edith Rosales-Alvarez / Jasmin Rettkowski / Josip Stefan Herman / Gabrijela Dumbović / Nina Cabezas-Wallscheid / Dominic Grün

    Genome Biology, Vol 24, Iss 1, Pp 1-

    2023  Volume 30

    Abstract: Abstract Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 ... ...

    Abstract Abstract Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.
    Keywords Gene expression noise ; Single-cell RNA sequencing ; Stem cell differentiation ; Cell sate variability ; Ageing ; Hematopoietic stem cells ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Unravelling the impact of aging on the human endothelial lncRNA transcriptome.

    Drekolia, Maria-Kyriaki / Talyan, Sweta / Cordellini Emídio, Rebeca / Boon, Reinier Abraham / Guenther, Stefan / Looso, Mario / Dumbović, Gabrijela / Bibli, Sofia-Iris

    Frontiers in genetics

    2022  Volume 13, Page(s) 1035380

    Abstract: The incidence and prevalence of cardiovascular disease is highest among the elderly. There is a need to further understand the mechanisms behind endothelial cell aging in order to achieve vascular rejuvenation and minimize the onset of age-related ... ...

    Abstract The incidence and prevalence of cardiovascular disease is highest among the elderly. There is a need to further understand the mechanisms behind endothelial cell aging in order to achieve vascular rejuvenation and minimize the onset of age-related vascular diseases. Long non-coding RNAs (lncRNAs) have been proposed to regulate numerous processes in the human genome, yet their function in vascular aging and their therapeutic potential remain largely unknown. This is primarily because the majority of studies investigating the impact of aging on lncRNA expression heavily rely on
    Language English
    Publishing date 2022-10-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2022.1035380
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Stimulated emission depletion (STED) super resolution imaging of RNA- and protein-containing domains in fixed cells.

    Dumbović, Gabrijela / Sanjuan, Xavier / Perucho, Manuel / Forcales, Sonia-V

    Methods (San Diego, Calif.)

    2020  Volume 187, Page(s) 68–76

    Abstract: Super resolution microscopy has changed our capability to visualize and understand spatial arrangements of RNA- and protein-containing domains in individual cells. In a previous study, we described a novel lncRNA, Tumor-associated NBL2 transcript (TNBL), ...

    Abstract Super resolution microscopy has changed our capability to visualize and understand spatial arrangements of RNA- and protein-containing domains in individual cells. In a previous study, we described a novel lncRNA, Tumor-associated NBL2 transcript (TNBL), which originates from a primate specific macrosatellite repeat. We aimed to describe several aspects of TNBL lncRNA, with one focus being pinpointing its precise location in the nucleus, as well as visualizing its interactions with proteins to deduce its functionality. Using a combination of STimulated Emission Depletion (STED) super resolution microscopy, single molecule RNA (smRNA) FISH against TNBL, and immunofluorescence against SAM68 perinucleolar body, we resolved the spatial complexity of the interaction between TNBL aggregates and SAM68 bodies at the perinucleolar region. Here, we describe protocols for a step-by-step optimized smRNA FISH/IF and STED imaging, detailing parameter settings, and three-dimensional data analysis of spatial positioning of subnuclear structures. These protocols can be employed for single-cell imaging of complex nuclear RNA-protein structures.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Cell Line, Tumor ; Cell Nucleus/metabolism ; DNA-Binding Proteins/genetics ; Epigenomics/methods ; Humans ; In Situ Hybridization, Fluorescence/methods ; Microscopy, Fluorescence/methods ; RNA, Long Noncoding/analysis ; RNA, Long Noncoding/metabolism ; RNA-Binding Proteins/genetics ; Single Molecule Imaging/methods ; Spatio-Temporal Analysis
    Chemical Substances Adaptor Proteins, Signal Transducing ; DNA-Binding Proteins ; KHDRBS1 protein, human ; RNA, Long Noncoding ; RNA-Binding Proteins
    Language English
    Publishing date 2020-04-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1066584-5
    ISSN 1095-9130 ; 1046-2023
    ISSN (online) 1095-9130
    ISSN 1046-2023
    DOI 10.1016/j.ymeth.2020.04.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3239: Show issues Location:
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  7. Article: Stimulated emission depletion (STED) super resolution imaging of RNA- and protein-containing domains in fixed cells

    Dumbović, Gabrijela / Sanjuan, Xavier / Perucho, Manuel / Forcales, Sonia-V

    Methods. 2020 Apr. 26,

    2020  

    Abstract: Super resolution microscopy has changed our capability to visualize and understand spatial arrangements of RNA- and protein-containing domains in individual cells. In a previous study, we described a novel lncRNA, Tumor-associated NBL2 transcript (TNBL), ...

    Abstract Super resolution microscopy has changed our capability to visualize and understand spatial arrangements of RNA- and protein-containing domains in individual cells. In a previous study, we described a novel lncRNA, Tumor-associated NBL2 transcript (TNBL), which originates from a primate specific macrosatellite repeat. We aimed to describe several aspects of TNBL lncRNA, with one focus being pinpointing its precise location in the nucleus, as well as visualizing its interactions with proteins to deduce its functionality. Using a combination of STimulated Emission Depletion (STED) super resolution microscopy, single molecule RNA (smRNA) FISH against TNBL, and immunofluorescence against SAM68 perinucleolar body, we resolved the spatial complexity of the interaction between TNBL aggregates and SAM68 bodies at the perinucleolar region. Here, we describe protocols for a step-by-step optimized smRNA FISH/IF and STED imaging, detailing parameter settings, and three-dimensional data analysis of spatial positioning of subnuclear structures. These protocols can be employed for single-cell imaging of complex nuclear RNA-protein structures.
    Keywords RNA ; fluorescence in situ hybridization ; fluorescent antibody technique ; image analysis ; microscopy ; proteins
    Language English
    Dates of publication 2020-0426
    Publishing place Elsevier Inc.
    Document type Article
    Note Pre-press version
    ZDB-ID 1066584-5
    ISSN 1095-9130 ; 1046-2023
    ISSN (online) 1095-9130
    ISSN 1046-2023
    DOI 10.1016/j.ymeth.2020.04.009
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Mosaic cis-regulatory evolution drives transcriptional partitioning of HERVH endogenous retrovirus in the human embryo

    Thomas A Carter / Manvendra Singh / Gabrijela Dumbović / Jason D Chobirko / John L Rinn / Cédric Feschotte

    eLife, Vol

    2022  Volume 11

    Abstract: The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal ... ...

    Abstract The human endogenous retrovirus type-H (HERVH) family is expressed in the preimplantation embryo. A subset of these elements are specifically transcribed in pluripotent stem cells where they appear to exert regulatory activities promoting self-renewal and pluripotency. How HERVH elements achieve such transcriptional specificity remains poorly understood. To uncover the sequence features underlying HERVH transcriptional activity, we performed a phyloregulatory analysis of the long terminal repeats (LTR7) of the HERVH family, which harbor its promoter, using a wealth of regulatory genomics data. We found that the family includes at least eight previously unrecognized subfamilies that have been active at different timepoints in primate evolution and display distinct expression patterns during human embryonic development. Notably, nearly all HERVH elements transcribed in ESCs belong to one of the youngest subfamilies we dubbed LTR7up. LTR7 sequence evolution was driven by a mixture of mutational processes, including point mutations, duplications, and multiple recombination events between subfamilies, that led to transcription factor binding motif modules characteristic of each subfamily. Using a reporter assay, we show that one such motif, a predicted SOX2/3 binding site unique to LTR7up, is essential for robust promoter activity in induced pluripotent stem cells. Together these findings illuminate the mechanisms by which HERVH diversified its expression pattern during evolution to colonize distinct cellular niches within the human embryo.
    Keywords endogenous retroviruses ; genomics ; primate evolution ; embryonic stem cells ; HERVH ; transposable elements ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury in murine males.

    Rogala, Sandra / Ali, Tamer / Melissari, Maria-Theodora / Währisch, Sandra / Schuster, Peggy / Sarre, Alexandre / Emídio, Rebeca Cordellini / Boettger, Thomas / Rogg, Eva-Maria / Kaur, Jaskiran / Krishnan, Jaya / Dumbović, Gabrijela / Dimmeler, Stefanie / Ounzain, Samir / Pedrazzini, Thierry / Herrmann, Bernhard G / Grote, Phillip

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 7024

    Abstract: After myocardial infarction in the adult heart the remaining, non-infarcted tissue adapts to compensate the loss of functional tissue. This adaptation requires changes in gene expression networks, which are mostly controlled by transcription regulating ... ...

    Abstract After myocardial infarction in the adult heart the remaining, non-infarcted tissue adapts to compensate the loss of functional tissue. This adaptation requires changes in gene expression networks, which are mostly controlled by transcription regulating proteins. Long non-coding transcripts (lncRNAs) are taking part in fine-tuning such gene programs. We describe and characterize the cardiomyocyte specific lncRNA Sweetheart RNA (Swhtr), an approximately 10 kb long transcript divergently expressed from the cardiac core transcription factor coding gene Nkx2-5. We show that Swhtr is dispensable for normal heart development and function but becomes essential for the tissue adaptation process after myocardial infarction in murine males. Re-expressing Swhtr from an exogenous locus rescues the Swhtr null phenotype. Genes that depend on Swhtr after cardiac stress are significantly occupied and therefore most likely regulated by NKX2-5. The Swhtr transcript interacts with NKX2-5 and disperses upon hypoxic stress in cardiomyocytes, indicating an auxiliary role of Swhtr for NKX2-5 function in tissue adaptation after myocardial injury.
    MeSH term(s) Male ; Mice ; Animals ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Myocytes, Cardiac/metabolism ; Cardiomegaly/genetics ; Cardiomegaly/metabolism ; Myocardial Infarction/metabolism ; Heart Injuries
    Chemical Substances RNA, Long Noncoding
    Language English
    Publishing date 2023-11-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-42760-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Publisher Correction: Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA is driven by intron retention.

    Dumbović, Gabrijela / Braunschweig, Ulrich / Langner, Heera K / Smallegan, Michael / Biayna, Josep / Hass, Evan P / Jastrzebska, Katarzyna / Blencowe, Benjamin / Cech, Thomas R / Caruthers, Marvin H / Rinn, John L

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 6189

    Language English
    Publishing date 2021-10-21
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-26492-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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