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  1. Article ; Online: Craving for Introns.

    Zaffagni, Michela / Kadener, Sebastian

    Molecular cell

    2019  Volume 73, Issue 6, Page(s) 1095–1096

    Abstract: Parenteau et al. (2019) and Morgan et al. (2019) showed that a subset of introns can work as non-coding RNAs that trap the spliceosome and decrease global splicing upon nutrient depletion in yeast, providing a new example of the functionality of introns, ...

    Abstract Parenteau et al. (2019) and Morgan et al. (2019) showed that a subset of introns can work as non-coding RNAs that trap the spliceosome and decrease global splicing upon nutrient depletion in yeast, providing a new example of the functionality of introns, molecules that were previously assumed to be useless.
    MeSH term(s) Introns ; RNA Splicing ; Saccharomyces cerevisiae ; Spliceosomes
    Language English
    Publishing date 2019-03-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2019.03.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome.

    Zaffagni, Michela / Harris, Jenna M / Patop, Ines L / Pamudurti, Nagarjuna Reddy / Nguyen, Sinead / Kadener, Sebastian

    bioRxiv : the preprint server for biology

    2022  

    Abstract: Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein ... ...

    Abstract Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1,000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of
    Language English
    Publishing date 2022-02-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.07.02.450964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome.

    Zaffagni, Michela / Harris, Jenna M / Patop, Ines L / Pamudurti, Nagarjuna Reddy / Nguyen, Sinead / Kadener, Sebastian

    eLife

    2022  Volume 11

    Abstract: Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein ... ...

    Abstract Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of
    MeSH term(s) COVID-19/genetics ; Exoribonucleases/metabolism ; Humans ; RNA, Viral/metabolism ; SARS-CoV-2 ; Transcriptome ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/metabolism ; Virus Replication/genetics
    Chemical Substances RNA, Viral ; Viral Nonstructural Proteins ; Exoribonucleases (EC 3.1.-)
    Language English
    Publishing date 2022-03-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.71945
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  4. Article ; Online: SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs.

    Rabin, Avigayel / Zaffagni, Michela / Ashwal-Fluss, Reut / Patop, Ines Lucia / Jajoo, Aarti / Shenzis, Shlomo / Carmel, Liran / Kadener, Sebastian

    Genome biology

    2021  Volume 22, Issue 1, Page(s) 277

    Abstract: Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that ...

    Abstract Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that SRCP is more sensitive than other individual pipelines and allows for more comprehensive quantification of a larger number of differentially expressed circRNAs. To facilitate the use of SRCP, we generate a comprehensive collection of validated circRNAs in five different organisms, including humans. We then utilize our approach and identify a subset of circRNAs bound to the miRNA-effector protein AGO2 in human brain samples.
    MeSH term(s) Animals ; Argonaute Proteins/metabolism ; Brain/metabolism ; Databases, Nucleic Acid ; Exoribonucleases ; Genomics ; Humans ; Mice ; Molecular Sequence Annotation ; RNA, Circular/analysis ; RNA, Circular/genetics ; RNA, Circular/metabolism ; RNA-Seq ; Rats ; Software
    Chemical Substances AGO2 protein, human ; Argonaute Proteins ; RNA, Circular ; Exoribonucleases (EC 3.1.-) ; ribonuclease R (EC 3.1.27.-)
    Language English
    Publishing date 2021-09-23
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-021-02497-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: SARS-CoV-2 Nsp14 mediates the effects of viral infection on the host cell transcriptome

    Michela Zaffagni / Jenna M Harris / Ines L Patop / Nagarjuna Reddy Pamudurti / Sinead Nguyen / Sebastian Kadener

    eLife, Vol

    2022  Volume 11

    Abstract: Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein ... ...

    Abstract Viral infection involves complex set of events orchestrated by multiple viral proteins. To identify functions of SARS-CoV-2 proteins, we performed transcriptomic analyses of cells expressing individual viral proteins. Expression of Nsp14, a protein involved in viral RNA replication, provoked a dramatic remodeling of the transcriptome that strongly resembled that observed following SARS-CoV-2 infection. Moreover, Nsp14 expression altered the splicing of more than 1000 genes and resulted in a dramatic increase in the number of circRNAs, which are linked to innate immunity. These effects were independent of the Nsp14 exonuclease activity and required the N7-guanine-methyltransferase domain of the protein. Activation of the NFkB pathway and increased expression of CXCL8 occurred early upon Nsp14 expression. We identified IMPDH2, which catalyzes the rate-limiting step of guanine nucleotides biosynthesis, as a key mediator of these effects. Nsp14 expression caused an increase in GTP cellular levels, and the effect of Nsp14 was strongly decreased in the presence of IMPDH2 inhibitors. Together, our data demonstrate an unknown role for Nsp14 with implications for therapy.
    Keywords SARS-CoV-2 ; Nsp14 ; IMPDH2 ; circRNA ; CXCL8 ; transcription ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: SRCP: a comprehensive pipeline for accurate annotation and quantification of circRNAs

    Rabin, Avigayel / Zaffagni, Michela / Ashwal-Fluss, Reut / Patop, Ines Lucia / Jajoo, Aarti / Shenzis, Shlomo / Carmel, Liran / Kadener, Sebastian

    Genome biology. 2021 Dec., v. 22, no. 1

    2021  

    Abstract: Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that ...

    Abstract Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that SRCP is more sensitive than other individual pipelines and allows for more comprehensive quantification of a larger number of differentially expressed circRNAs. To facilitate the use of SRCP, we generate a comprehensive collection of validated circRNAs in five different organisms, including humans. We then utilize our approach and identify a subset of circRNAs bound to the miRNA-effector protein AGO2 in human brain samples.
    Keywords brain ; genome ; humans
    Language English
    Dates of publication 2021-12
    Size p. 277.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-021-02497-7
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: SRCP

    Avigayel Rabin / Michela Zaffagni / Reut Ashwal-Fluss / Ines Lucia Patop / Aarti Jajoo / Shlomo Shenzis / Liran Carmel / Sebastian Kadener

    Genome Biology, Vol 22, Iss 1, Pp 1-

    a comprehensive pipeline for accurate annotation and quantification of circRNAs

    2021  Volume 26

    Abstract: Abstract Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We ... ...

    Abstract Abstract Here we describe a new integrative approach for accurate annotation and quantification of circRNAs named Short Read circRNA Pipeline (SRCP). Our strategy involves two steps: annotation of validated circRNAs followed by a quantification step. We show that SRCP is more sensitive than other individual pipelines and allows for more comprehensive quantification of a larger number of differentially expressed circRNAs. To facilitate the use of SRCP, we generate a comprehensive collection of validated circRNAs in five different organisms, including humans. We then utilize our approach and identify a subset of circRNAs bound to the miRNA-effector protein AGO2 in human brain samples.
    Keywords Circular RNA ; CircRNAs ; RNA metabolism ; Splicing ; Pipeline ; AGO2 ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Synthesis and anticancer activity of novel water soluble benzimidazole carbamates.

    Cheong, Jae Eun / Zaffagni, Michela / Chung, Ivy / Xu, Yingjie / Wang, Yiqiang / Jernigan, Finith E / Zetter, Bruce R / Sun, Lijun

    European journal of medicinal chemistry

    2018  Volume 144, Page(s) 372–385

    Abstract: Metastases account for more than 90% of all cancer deaths and respond poorly to most therapies. There remains an urgent need for new therapeutic modalities for the treatment of advanced metastatic cancers. The benzimidazole methylcarbamate drugs, ... ...

    Abstract Metastases account for more than 90% of all cancer deaths and respond poorly to most therapies. There remains an urgent need for new therapeutic modalities for the treatment of advanced metastatic cancers. The benzimidazole methylcarbamate drugs, commonly used as anti-helmitics, have been suggested to have anticancer activity, but progress has been stalled by their poor water solubility and poor suitability for systemic delivery to disseminated cancers. We synthesized and characterized the anticancer activity of novel benzimidazoles containing an oxetane or an amine group to enhance solubility. Among them, the novel oxetanyl substituted compound 18 demonstrated significant cytotoxicity toward a variety of cancer cell types including prostate, lung, and ovarian cancers with strong activity toward highly aggressive cancer lines (IC
    MeSH term(s) Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Benzimidazoles/chemical synthesis ; Benzimidazoles/chemistry ; Benzimidazoles/pharmacology ; Carbamates/chemical synthesis ; Carbamates/chemistry ; Carbamates/pharmacology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Dose-Response Relationship, Drug ; Humans ; Male ; Mice ; Molecular Docking Simulation ; Molecular Structure ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/pathology ; Solubility ; Structure-Activity Relationship ; Tumor Cells, Cultured ; Water/chemistry
    Chemical Substances Antineoplastic Agents ; Benzimidazoles ; Carbamates ; Water (059QF0KO0R)
    Language English
    Publishing date 2018-01-20
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2017.11.037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Intra-epithelial non-canonical Activin A signaling safeguards prostate progenitor quiescence.

    Cambuli, Francesco / Foletto, Veronica / Alaimo, Alessandro / De Felice, Dario / Gandolfi, Francesco / Palumbieri, Maria Dilia / Zaffagni, Michela / Genovesi, Sacha / Lorenzoni, Marco / Celotti, Martina / Bertossio, Emiliana / Mazzero, Giosuè / Bertossi, Arianna / Bisio, Alessandra / Berardinelli, Francesco / Antoccia, Antonio / Gaspari, Marco / Barbareschi, Mattia / Fiorentino, Michelangelo /
    Shen, Michael M / Loda, Massimo / Romanel, Alessandro / Lunardi, Andrea

    EMBO reports

    2022  Volume 23, Issue 5, Page(s) e54049

    Abstract: The healthy prostate is a relatively quiescent tissue. Yet, prostate epithelium overgrowth is a common condition during aging, associated with urinary dysfunction and tumorigenesis. For over thirty years, TGF-β ligands have been known to induce ... ...

    Abstract The healthy prostate is a relatively quiescent tissue. Yet, prostate epithelium overgrowth is a common condition during aging, associated with urinary dysfunction and tumorigenesis. For over thirty years, TGF-β ligands have been known to induce cytostasis in a variety of epithelia, but the intracellular pathway mediating this signal in the prostate, and its relevance for quiescence, have remained elusive. Here, using mouse prostate organoids to model epithelial progenitors, we find that intra-epithelial non-canonical Activin A signaling inhibits cell proliferation in a Smad-independent manner. Mechanistically, Activin A triggers Tak1 and p38 ΜAPK activity, leading to p16 and p21 nuclear import. Spontaneous evasion from this quiescent state occurs upon prolonged culture, due to reduced Activin A secretion, a condition associated with DNA replication stress and aneuploidy. Organoids capable to escape quiescence in vitro are also able to implant with increased frequency into immunocompetent mice. This study demonstrates that non-canonical Activin A signaling safeguards epithelial quiescence in the healthy prostate, with potential implications for the understanding of cancer initiation, and the development of therapies targeting quiescent tumor progenitors.
    MeSH term(s) Activins/metabolism ; Animals ; Male ; Mice ; Prostate/metabolism ; Signal Transduction ; Transforming Growth Factor beta/metabolism
    Chemical Substances Transforming Growth Factor beta ; activin A ; Activins (104625-48-1)
    Language English
    Publishing date 2022-03-07
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202154049
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