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  1. Artikel ; Online: RNA structure profiling at single-cell resolution reveals new determinants of cell identity.

    Wang, Jiaxu / Zhang, Yu / Zhang, Tong / Tan, Wen Ting / Lambert, Finnlay / Darmawan, Jefferson / Huber, Roland / Wan, Yue

    Nature methods

    2024  Band 21, Heft 3, Seite(n) 411–422

    Abstract: RNA structure is critical for multiple steps in gene regulation. However, how the structures of transcripts differ both within and between individual cells is unknown. Here we develop a SHAPE-inspired method called single-cell structure probing of RNA ... ...

    Abstract RNA structure is critical for multiple steps in gene regulation. However, how the structures of transcripts differ both within and between individual cells is unknown. Here we develop a SHAPE-inspired method called single-cell structure probing of RNA transcripts that enables simultaneous determination of transcript secondary structure and abundance at single-cell resolution. We apply single-cell structure probing of RNA transcripts to human embryonic stem cells and differentiating neurons. Remarkably, RNA structure is more homogeneous in human embryonic stem cells compared with neurons, with the greatest homogeneity found in coding regions. More extensive heterogeneity is found within 3' untranslated regions and is determined by specific RNA-binding proteins. Overall RNA structure profiles better discriminate cell type identity and differentiation stage than gene expression profiles alone. We further discover a cell-type variable region of 18S ribosomal RNA that is associated with cell cycle and translation control. Our method opens the door to the systematic characterization of RNA structure-function relationships at single-cell resolution.
    Mesh-Begriff(e) Humans ; RNA/genetics ; RNA/chemistry ; RNA, Messenger/genetics ; Base Sequence ; Nucleic Acid Conformation ; Cell Differentiation
    Chemische Substanzen RNA (63231-63-0) ; RNA, Messenger
    Sprache Englisch
    Erscheinungsdatum 2024-01-04
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-023-02128-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Translational control of furina by an RNA regulon is important for left-right patterning, heart morphogenesis and cardiac valve function.

    Nagorska, Agnieszka / Zaucker, Andreas / Lambert, Finnlay / Inman, Angus / Toral-Perez, Sara / Gorodkin, Jan / Wan, Yue / Smutny, Michael / Sampath, Karuna

    Development (Cambridge, England)

    2023  Band 150, Heft 23

    Abstract: Heart development is a complex process that requires asymmetric positioning of the heart, cardiac growth and valve morphogenesis. The mechanisms controlling heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA ... ...

    Abstract Heart development is a complex process that requires asymmetric positioning of the heart, cardiac growth and valve morphogenesis. The mechanisms controlling heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA functions in heart development across vertebrates. How FurinA activity is regulated during heart development is unknown. Through computational analysis of the zebrafish transcriptome, we identified an RNA motif in a variant FurinA transcript harbouring a long 3' untranslated region (3'UTR). The alternative 3'UTR furina isoform is expressed prior to organ positioning. Somatic deletions in the furina 3'UTR lead to embryonic left-right patterning defects. Reporter localisation and RNA-binding assays show that the furina 3'UTR forms complexes with the conserved RNA-binding translational repressor, Ybx1. Conditional ybx1 mutant embryos show premature and increased Furin reporter expression, abnormal cardiac morphogenesis and looping defects. Mutant ybx1 hearts have an expanded atrioventricular canal, abnormal sino-atrial valves and retrograde blood flow from the ventricle to the atrium. This is similar to observations in humans with heart valve regurgitation. Thus, the furina 3'UTR element/Ybx1 regulon is important for translational repression of FurinA and regulation of heart development.
    Mesh-Begriff(e) Animals ; Humans ; Zebrafish ; 3' Untranslated Regions ; Regulon/genetics ; Morphogenesis/genetics ; Heart Valves ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism ; Proprotein Convertases/genetics ; Proprotein Convertases/metabolism
    Chemische Substanzen 3' Untranslated Regions ; FurinA protein, zebrafish (EC 3.4.-) ; Zebrafish Proteins ; Proprotein Convertases (EC 3.4.21.-)
    Sprache Englisch
    Erscheinungsdatum 2023-11-30
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.201657
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks.

    Wang, Jiaxu / Zhang, Tong / Yu, Zhang / Tan, Wen Ting / Wen, Ming / Shen, Yang / Lambert, Finnlay R P / Huber, Roland G / Wan, Yue

    Molecular cell

    2021  Band 81, Heft 23, Seite(n) 4942–4953.e8

    Abstract: The distribution, dynamics, and function of RNA structures in human development are under-explored. Here, we systematically assayed RNA structural dynamics and their relationship with gene expression, translation, and decay during human neurogenesis. We ... ...

    Abstract The distribution, dynamics, and function of RNA structures in human development are under-explored. Here, we systematically assayed RNA structural dynamics and their relationship with gene expression, translation, and decay during human neurogenesis. We observed that the human ESC transcriptome is globally more structurally accessible than differentiated cells and undergoes extensive RNA structure changes, particularly in the 3' UTR. Additionally, RNA structure changes during differentiation are associated with translation and decay. We observed that RBP and miRNA binding is associated with RNA structural changes during early neuronal differentiation, and splicing is associated during later neuronal differentiation. Furthermore, our analysis suggests that RBPs are major factors in structure remodeling and co-regulate additional RBPs and miRNAs through structure. We demonstrated an example of this by showing that PUM2-induced structure changes on LIN28A enable miR-30 binding. This study deepens our understanding of the widespread and complex role of RNA-based gene regulation during human development.
    Mesh-Begriff(e) 3' Untranslated Regions ; Cell Differentiation ; Cluster Analysis ; Gene Regulatory Networks ; Genetic Techniques ; Genome-Wide Association Study ; HEK293 Cells ; Humans ; MicroRNAs/metabolism ; Models, Statistical ; Neurogenesis ; Neurons/metabolism ; Neurons/physiology ; Nucleic Acid Conformation ; RNA/analysis ; RNA Splicing ; RNA-Binding Proteins/metabolism ; Substrate Specificity ; Systems Biology ; Transcription, Genetic ; Transcriptome
    Chemische Substanzen 3' Untranslated Regions ; Lin28A protein, human ; MIRN30a microRNA, human ; MicroRNAs ; RNA-Binding Proteins ; RNA (63231-63-0)
    Sprache Englisch
    Erscheinungsdatum 2021-10-15
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.09.027
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks

    Wang, Jiaxu / Zhang, Tong / Yu, Zhang / Tan, Wen Ting / Wen, Ming / Shen, Yang / Lambert, Finnlay R.P. / Huber, Roland G. / Wan, Yue

    Molecular cell. 2021 Dec. 02, v. 81, no. 23

    2021  

    Abstract: The distribution, dynamics, and function of RNA structures in human development are under-explored. Here, we systematically assayed RNA structural dynamics and their relationship with gene expression, translation, and decay during human neurogenesis. We ... ...

    Abstract The distribution, dynamics, and function of RNA structures in human development are under-explored. Here, we systematically assayed RNA structural dynamics and their relationship with gene expression, translation, and decay during human neurogenesis. We observed that the human ESC transcriptome is globally more structurally accessible than differentiated cells and undergoes extensive RNA structure changes, particularly in the 3′ UTR. Additionally, RNA structure changes during differentiation are associated with translation and decay. We observed that RBP and miRNA binding is associated with RNA structural changes during early neuronal differentiation, and splicing is associated during later neuronal differentiation. Furthermore, our analysis suggests that RBPs are major factors in structure remodeling and co-regulate additional RBPs and miRNAs through structure. We demonstrated an example of this by showing that PUM2-induced structure changes on LIN28A enable miR-30 binding. This study deepens our understanding of the widespread and complex role of RNA-based gene regulation during human development.
    Schlagwörter gene expression ; genes ; human development ; humans ; microRNA ; neurogenesis ; neurons ; transcriptome
    Sprache Englisch
    Erscheinungsverlauf 2021-1202
    Umfang p. 4942-4953.e8.
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.09.027
    Datenquelle NAL Katalog (AGRICOLA)

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  5. Artikel ; Online: Publisher Correction: Determination of isoform-specific RNA structure with nanopore long reads.

    Aw, Jong Ghut Ashley / Lim, Shaun W / Wang, Jia Xu / Lambert, Finnlay R P / Tan, Wen Ting / Shen, Yang / Zhang, Yu / Kaewsapsak, Pornchai / Li, Chenhao / Ng, Sarah B / Vardy, Leah A / Tan, Meng How / Nagarajan, Niranjan / Wan, Yue

    Nature biotechnology

    2021  Band 39, Heft 4, Seite(n) 520

    Sprache Englisch
    Erscheinungsdatum 2021-03-23
    Erscheinungsland United States
    Dokumenttyp Published Erratum
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-021-00889-5
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Determination of isoform-specific RNA structure with nanopore long reads.

    Aw, Jong Ghut Ashley / Lim, Shaun W / Wang, Jia Xu / Lambert, Finnlay R P / Tan, Wen Ting / Shen, Yang / Zhang, Yu / Kaewsapsak, Pornchai / Li, Chenhao / Ng, Sarah B / Vardy, Leah A / Tan, Meng How / Nagarajan, Niranjan / Wan, Yue

    Nature biotechnology

    2020  Band 39, Heft 3, Seite(n) 336–346

    Abstract: Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure ... ...

    Abstract Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. PORE-cupine also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants. We show that shared sequences in different transcript isoforms of the same gene can fold into different structures, highlighting the importance of long-read sequencing for obtaining phase information. We also demonstrate that structural differences between transcript isoforms of the same gene lead to differences in translation efficiency. By revealing isoform-specific RNA structure, PORE-cupine will deepen understanding of the role of structures in controlling gene regulation.
    Mesh-Begriff(e) Human Embryonic Stem Cells/metabolism ; Humans ; Isomerism ; Nanopore Sequencing/methods ; Nucleic Acid Conformation ; RNA/chemistry ; RNA/genetics ; Sequence Analysis, RNA/methods ; Tetrahymena/genetics ; Transcriptome
    Chemische Substanzen RNA (63231-63-0)
    Sprache Englisch
    Erscheinungsdatum 2020-10-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-020-0712-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Author Correction: Determination of isoform-specific RNA structure with nanopore long reads.

    Aw, Jong Ghut Ashley / Lim, Shaun W / Wang, Jia Xu / Lambert, Finnlay R P / Tan, Wen Ting / Shen, Yang / Zhang, Yu / Kaewsapsak, Pornchai / Li, Chenhao / Ng, Sarah B / Vardy, Leah A / Tan, Meng How / Nagarajan, Niranjan / Wan, Yue

    Nature biotechnology

    2020  Band 39, Heft 3, Seite(n) 387

    Sprache Englisch
    Erscheinungsdatum 2020-11-13
    Erscheinungsland United States
    Dokumenttyp Published Erratum
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-020-00755-w
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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