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  1. Article ; Online: An elusive debate on the evidence for RNA editing in SARS-CoV-2.

    Mattiuz, Giorgio / Di Giorgio, Salvatore / Conticello, Silvestro G

    RNA biology

    2024  Volume 21, Issue 1, Page(s) 1–2

    MeSH term(s) Humans ; SARS-CoV-2/genetics ; RNA Editing ; COVID-19 ; RNA, Viral/genetics
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2159587-2
    ISSN 1555-8584 ; 1555-8584
    ISSN (online) 1555-8584
    ISSN 1555-8584
    DOI 10.1080/15476286.2024.2321032
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Modified Cas9-Guided Oxford Nanopore Technology Sequencing Uncovers Single and Multiple Transgene Insertion Sites in a Zebrafish Melanoma Model.

    De Paolo, Raffaella / Munagala, Uday / Cucco, Francesco / Sarti, Samanta / Pitto, Letizia / Martignano, Filippo / Conticello, Silvestro G / Poliseno, Laura

    The CRISPR journal

    2023  Volume 6, Issue 6, Page(s) 489–492

    MeSH term(s) Animals ; CRISPR-Cas Systems/genetics ; Melanoma/genetics ; Nanopores ; Zebrafish/genetics ; Gene Editing
    Language English
    Publishing date 2023-12-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3017891-5
    ISSN 2573-1602 ; 2573-1599
    ISSN (online) 2573-1602
    ISSN 2573-1599
    DOI 10.1089/crispr.2023.0062
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Live-Cell Quantification of APOBEC1-Mediated RNA Editing: A Comparison of RNA Editing Assays.

    Chieca, Martina / Torrini, Serena / Conticello, Silvestro G

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2181, Page(s) 69–81

    Abstract: APOBEC1 is a member of the AID/APOBECs, a group of deaminases responsible for the editing of C>U in both DNA and RNA. APOBEC1 is physiologically involved in C>U RNA editing: while hundreds of targets have been discovered in mice, in humans the only well- ... ...

    Abstract APOBEC1 is a member of the AID/APOBECs, a group of deaminases responsible for the editing of C>U in both DNA and RNA. APOBEC1 is physiologically involved in C>U RNA editing: while hundreds of targets have been discovered in mice, in humans the only well-characterized target of APOBEC1 is the apolipoprotein B (ApoB) transcript. APOBEC1 edits a CAA codon into a stop codon, which causes the translation of a truncated form of ApoB. A number of assays have been developed to investigate this process. Early assays, poisoned primer extension and Sanger sequencing, have focused on accuracy and sensitivity but rely on extraction of the RNA from tissues and cells. More recently, the need to visualize the RNA editing process directly in live cells have led to the development of fluorescence-based tools. These assays detect RNA editing through reporters whose editing causes a change in cellular localization or a change in fluorescent properties. Here we review the available assays to quantify RNA editing, and we present the protocol for cytofluorimetric analysis using a double-fluorescent reporter.
    MeSH term(s) APOBEC-1 Deaminase/genetics ; APOBEC-1 Deaminase/metabolism ; Computational Biology/methods ; Cytidine/chemistry ; Cytidine/genetics ; Genes, Reporter ; HEK293 Cells ; Hep G2 Cells ; High-Throughput Nucleotide Sequencing ; Humans ; RNA Editing/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Subcellular Fractions/metabolism ; Uridine/chemistry ; Uridine/genetics
    Chemical Substances RNA, Messenger ; Cytidine (5CSZ8459RP) ; APOBEC-1 Deaminase (EC 3.5.4.36) ; Uridine (WHI7HQ7H85)
    Language English
    Publishing date 2020-07-29
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-0787-9_5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Harnessing mutation: The best of two worlds.

    Conticello, Silvestro G / Rada, Cristina

    Science (New York, N.Y.)

    2016  Volume 353, Issue 6305, Page(s) 1206–1207

    MeSH term(s) Humans ; Mutation
    Language English
    Publishing date 2016-10-05
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aai8233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Creative deaminases, self-inflicted damage, and genome evolution.

    Conticello, Silvestro G

    Annals of the New York Academy of Sciences

    2012  Volume 1267, Page(s) 79–85

    Abstract: Organisms minimize genetic damage through complex pathways of DNA repair. Yet a gene family--the AID/APOBECs--has evolved in vertebrates with the sole purpose of producing targeted damage in DNA/RNA molecules through cytosine deamination. They likely ... ...

    Abstract Organisms minimize genetic damage through complex pathways of DNA repair. Yet a gene family--the AID/APOBECs--has evolved in vertebrates with the sole purpose of producing targeted damage in DNA/RNA molecules through cytosine deamination. They likely originated from deaminases involved in A>I editing in tRNAs. AID, the archetypal AID/APOBEC, is the trigger of the somatic diversification processes of the antibody genes. Its homologs may have been associated with the immune system even before the evolution of the antibody genes. The APOBEC3s, arising from duplication of AID, are involved in the restriction of exogenous/endogenous threats such as retroviruses and mobile elements. Another family member, APOBEC1, has (re)acquired the ability to target RNA while maintaining its ability to act on DNA. The AID/APOBECs have shaped the evolution of vertebrate genomes, but their ability to mutate nucleic acids is a double-edged sword: AID is a key player in lymphoproliferative diseases by triggering mutations and chromosomal translocations in B cells, and there is increasing evidence suggesting that other AID/APOBECs could be involved in cancer development as well.
    MeSH term(s) Animals ; DNA Damage ; Evolution, Molecular ; Genome, Human ; Humans ; Immunoglobulins/genetics ; Mutagenesis ; Mutation ; Neoplasms/genetics ; Nucleoside Deaminases/genetics ; Nucleoside Deaminases/physiology ; Phylogeny ; RNA/genetics ; RNA/metabolism ; RNA Editing
    Chemical Substances Immunoglobulins ; RNA (63231-63-0) ; Nucleoside Deaminases (EC 3.5.4.-)
    Language English
    Publishing date 2012-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/j.1749-6632.2012.06614.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: COVID-19 annual update: a narrative review.

    Biancolella, Michela / Colona, Vito Luigi / Luzzatto, Lucio / Watt, Jessica Lee / Mattiuz, Giorgio / Conticello, Silvestro G / Kaminski, Naftali / Mehrian-Shai, Ruty / Ko, Albert I / Gonsalves, Gregg S / Vasiliou, Vasilis / Novelli, Giuseppe / Reichardt, Juergen K V

    Human genomics

    2023  Volume 17, Issue 1, Page(s) 68

    Abstract: Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we ... ...

    Abstract Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we give an outlook on state-of-the-art therapeutical approaches, as the pandemic is gradually transitioning to an endemic situation. The sequencing and characterization of rare alleles in different populations has made it possible to identify numerous genes that affect either susceptibility to COVID-19 or the severity of the disease. These findings provide a beginning to new avenues and pan-ethnic therapeutic approaches, as well as to potential genetic screening protocols. The causative virus, SARS-CoV-2, is still in the spotlight, but novel threatening virus could appear anywhere at any time. Therefore, continued vigilance and further research is warranted. We also note emphatically that to prevent future pandemics and other world-wide health crises, it is imperative to capitalize on what we have learnt from COVID-19: specifically, regarding its origins, the world's response, and insufficient preparedness. This requires unprecedented international collaboration and timely data sharing for the coordination of effective response and the rapid implementation of containment measures.
    MeSH term(s) Humans ; COVID-19/therapy ; SARS-CoV-2/genetics ; Evolution, Molecular ; Genome-Wide Association Study ; Genomics
    Language English
    Publishing date 2023-07-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2147618-4
    ISSN 1479-7364 ; 1479-7364
    ISSN (online) 1479-7364
    ISSN 1479-7364
    DOI 10.1186/s40246-023-00515-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Identification and characterization of novel ETV4 splice variants in prostate cancer.

    Cosi, Irene / Moccia, Annalisa / Pescucci, Chiara / Munagala, Uday / Di Giorgio, Salvatore / Sineo, Irene / Conticello, Silvestro G / Notaro, Rosario / De Angioletti, Maria

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 5267

    Abstract: ETV4, one of ETS proteins overexpressed in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies a series of previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines. Their ...

    Abstract ETV4, one of ETS proteins overexpressed in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies a series of previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines. Their expression has been validated using several unbiased techniques, including Nanopore sequencing. Most of these transcripts originate from an in-frame exon skipping and, thus, are expected to be translated into ETV4 protein isoforms. Functional analysis of the most abundant among these isoforms shows that they still bear an activity, namely a reduced ability to promote proliferation and a residual ability to regulate the transcription of ETV4 target genes. Alternatively spliced genes are common in cancer cells: an analysis of the TCGA dataset confirms the abundance of these novel ETV4 transcripts in prostate tumors, in contrast to peritumoral tissues. Since none of their translated isoforms have acquired a higher oncogenic potential, such abundance is likely to reflect the tumor deranged splicing machinery. However, it is also possible that their interaction with the canonical variants may contribute to the biology and the clinics of prostate cancer. Further investigations are needed to elucidate the biological role of these ETV4 transcripts and of their putative isoforms.
    MeSH term(s) Humans ; Male ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Prostatic Neoplasms/pathology ; Proto-Oncogene Proteins/metabolism ; Proto-Oncogene Proteins c-ets/genetics ; Proto-Oncogene Proteins c-ets/metabolism
    Chemical Substances ETV4 protein, human ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-ets
    Language English
    Publishing date 2023-03-31
    Publishing country England
    Document type Journal Article ; 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/s41598-023-29484-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Flow-cytometric visualization of C>U mRNA editing reveals the dynamics of the process in live cells.

    Severi, Francesco / Conticello, Silvestro G

    RNA biology

    2015  Volume 12, Issue 4, Page(s) 389–397

    Abstract: APOBEC1 is the catalytic subunit of the complex that edits ApolipoproteinB (ApoB) mRNA, which specifically deaminates cytidine 6666 to uracil in the human transcript. The editing leads to the generation of a stop codon, resulting in the synthesis of a ... ...

    Abstract APOBEC1 is the catalytic subunit of the complex that edits ApolipoproteinB (ApoB) mRNA, which specifically deaminates cytidine 6666 to uracil in the human transcript. The editing leads to the generation of a stop codon, resulting in the synthesis of a truncated form of ApoB. We have developed a method to quantitatively assay ApoB RNA editing in live cells by using a double fluorescent mCherry-EGFP chimera containing a ∼ 300 bp fragment encompassing the region of ApoB subject to RNA editing. Coexpression of APOBEC1 together with this chimera causes specific RNA editing of the ApoB fragment. The insertion of a stop codon between the mCherry and EGFP thus induces the loss of EGFP fluorescence. Using this method we analyze the dynamics of APOBEC1-dependent RNA editing under various conditions. Namely we show the interplay of APOBEC1 with known interactors (ACF, hnRNP-C1, GRY-RBP) in cells that are RNA editing-proficient (HuH-7) or -deficient (HEK-293T), and the effects of restricted cellular localization of APOBEC1 on the efficiency of the editing. Furthermore, our approach is effective in assaying the induction of RNA editing in Caco-2, a cellular model physiologically capable of ApoB RNA editing.
    MeSH term(s) Animals ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Cytosine/metabolism ; Flow Cytometry/methods ; Humans ; RNA Editing ; RNA, Messenger/metabolism ; Rats ; Uracil/metabolism
    Chemical Substances RNA, Messenger ; Uracil (56HH86ZVCT) ; Cytosine (8J337D1HZY)
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1555-8584
    ISSN (online) 1555-8584
    DOI 10.1080/15476286.2015.1026033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2.

    Di Giorgio, Salvatore / Martignano, Filippo / Torcia, Maria Gabriella / Mattiuz, Giorgio / Conticello, Silvestro G

    Science advances

    2020  Volume 6, Issue 25, Page(s) eabb5813

    Abstract: The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it ... ...

    Abstract The COVID-19 outbreak has become a global health risk, and understanding the response of the host to the SARS-CoV-2 virus will help to combat the disease. RNA editing by host deaminases is an innate restriction process to counter virus infection, but it is not yet known whether this process operates against coronaviruses. Here, we analyze RNA sequences from bronchoalveolar lavage fluids obtained from coronavirus-infected patients. We identify nucleotide changes that may be signatures of RNA editing: adenosine-to-inosine changes from ADAR deaminases and cytosine-to-uracil changes from APOBEC deaminases. Mutational analysis of genomes from different strains of Coronaviridae from human hosts reveals mutational patterns consistent with those observed in the transcriptomic data. However, the reduced ADAR signature in these data raises the possibility that ADARs might be more effective than APOBECs in restricting viral propagation. Our results thus suggest that both APOBECs and ADARs are involved in coronavirus genome editing, a process that may shape the fate of both virus and patient.
    MeSH term(s) APOBEC Deaminases/genetics ; APOBEC Deaminases/metabolism ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Base Sequence/genetics ; Betacoronavirus/genetics ; Betacoronavirus/metabolism ; Bronchoalveolar Lavage Fluid/virology ; COVID-19 ; Coronavirus Infections/genetics ; Coronavirus Infections/virology ; Genome, Viral/genetics ; Host-Pathogen Interactions/genetics ; Humans ; Mutation Rate ; Nucleotides/genetics ; Nucleotides/metabolism ; Pandemics ; Pneumonia, Viral/genetics ; Pneumonia, Viral/virology ; RNA Editing/genetics ; RNA, Viral/genetics ; SARS-CoV-2 ; Transcriptome ; Virus Replication/genetics
    Chemical Substances Nucleotides ; RNA, Viral ; ADA protein, human (EC 3.5.4.4) ; Adenosine Deaminase (EC 3.5.4.4) ; APOBEC Deaminases (EC 3.5.4.5)
    Keywords covid19
    Language English
    Publishing date 2020-06-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abb5813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Identification and characterization of novel ETV4 splice variants in prostate cancer

    Irene Cosi / Annalisa Moccia / Chiara Pescucci / Uday Munagala / Salvatore Di Giorgio / Irene Sineo / Silvestro G. Conticello / Rosario Notaro / Maria De Angioletti

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 14

    Abstract: Abstract ETV4, one of ETS proteins overexpressed in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies a series of previously unknown ETV4 alternatively spliced transcripts in human prostate cell ... ...

    Abstract Abstract ETV4, one of ETS proteins overexpressed in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies a series of previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines. Their expression has been validated using several unbiased techniques, including Nanopore sequencing. Most of these transcripts originate from an in-frame exon skipping and, thus, are expected to be translated into ETV4 protein isoforms. Functional analysis of the most abundant among these isoforms shows that they still bear an activity, namely a reduced ability to promote proliferation and a residual ability to regulate the transcription of ETV4 target genes. Alternatively spliced genes are common in cancer cells: an analysis of the TCGA dataset confirms the abundance of these novel ETV4 transcripts in prostate tumors, in contrast to peritumoral tissues. Since none of their translated isoforms have acquired a higher oncogenic potential, such abundance is likely to reflect the tumor deranged splicing machinery. However, it is also possible that their interaction with the canonical variants may contribute to the biology and the clinics of prostate cancer. Further investigations are needed to elucidate the biological role of these ETV4 transcripts and of their putative isoforms.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572 ; 570
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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