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  1. Article ; Online: Depletion of Mettl3 in cholinergic neurons causes adult-onset neuromuscular degeneration.

    Dermentzaki, Georgia / Furlan, Mattia / Tanaka, Iris / Leonardi, Tommaso / Rinchetti, Paola / Passos, Patricia M S / Bastos, Alliny / Ayala, Yuna M / Hanna, Jacob H / Przedborski, Serge / Bonanomi, Dario / Pelizzola, Mattia / Lotti, Francesco

    Cell reports

    2024  Volume 43, Issue 4, Page(s) 113999

    Abstract: Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA's fate, and defects in RNA processing are critical determinants of MN ... ...

    Abstract Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA's fate, and defects in RNA processing are critical determinants of MN degeneration. N
    MeSH term(s) Animals ; Humans ; Mice ; Adenosine/metabolism ; Adenosine/analogs & derivatives ; Amyotrophic Lateral Sclerosis/metabolism ; Amyotrophic Lateral Sclerosis/pathology ; Amyotrophic Lateral Sclerosis/genetics ; Cholinergic Neurons/metabolism ; Cholinergic Neurons/pathology ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/genetics ; Methyltransferases/metabolism ; Methyltransferases/genetics ; Motor Neurons/metabolism ; Motor Neurons/pathology ; Neuromuscular Diseases/metabolism ; Neuromuscular Diseases/pathology
    Chemical Substances Adenosine (K72T3FS567) ; DNA-Binding Proteins ; Methyltransferases (EC 2.1.1.-) ; METTL3 protein, human (EC 2.1.1.62) ; Mettl3 protein, mouse (EC 2.1.1.-) ; N-methyladenosine (CLE6G00625)
    Language English
    Publishing date 2024-03-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.113999
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Direct RNA Sequencing for the Study of Synthesis, Processing, and Degradation of Modified Transcripts.

    Furlan, Mattia / Tanaka, Iris / Leonardi, Tommaso / de Pretis, Stefano / Pelizzola, Mattia

    Frontiers in genetics

    2020  Volume 11, Page(s) 394

    Abstract: It has been known for a few decades that transcripts can be marked by dozens of different modifications. Yet, we are just at the beginning of charting these marks and understanding their functional impact. High-quality methods were developed for the ... ...

    Abstract It has been known for a few decades that transcripts can be marked by dozens of different modifications. Yet, we are just at the beginning of charting these marks and understanding their functional impact. High-quality methods were developed for the profiling of some of these marks, and approaches to finely study their impact on specific phases of the RNA life-cycle are available, including RNA metabolic labeling. Thanks to these improvements, the most abundant marks, including N
    Keywords covid19
    Language English
    Publishing date 2020-04-28
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2020.00394
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: ZRANB2 and SYF2-mediated splicing programs converging on ECT2 are involved in breast cancer cell resistance to doxorubicin.

    Tanaka, Iris / Chakraborty, Alina / Saulnier, Olivier / Benoit-Pilven, Clara / Vacher, Sophie / Labiod, Dalila / Lam, Eric W F / Bièche, Ivan / Delattre, Olivier / Pouzoulet, Frédéric / Auboeuf, Didier / Vagner, Stéphan / Dutertre, Martin

    Nucleic acids research

    2020  Volume 48, Issue 5, Page(s) 2676–2693

    Abstract: Besides analyses of specific alternative splicing (AS) variants, little is known about AS regulatory pathways and programs involved in anticancer drug resistance. Doxorubicin is widely used in breast cancer chemotherapy. Here, we identified 1723 AS ... ...

    Abstract Besides analyses of specific alternative splicing (AS) variants, little is known about AS regulatory pathways and programs involved in anticancer drug resistance. Doxorubicin is widely used in breast cancer chemotherapy. Here, we identified 1723 AS events and 41 splicing factors regulated in a breast cancer cell model of acquired resistance to doxorubicin. An RNAi screen on splicing factors identified the little studied ZRANB2 and SYF2, whose depletion partially reversed doxorubicin resistance. By RNAi and RNA-seq in resistant cells, we found that the AS programs controlled by ZRANB2 and SYF2 were enriched in resistance-associated AS events, and converged on the ECT2 splice variant including exon 5 (ECT2-Ex5+). Both ZRANB2 and SYF2 were found associated with ECT2 pre-messenger RNA, and ECT2-Ex5+ isoform depletion reduced doxorubicin resistance. Following doxorubicin treatment, resistant cells accumulated in S phase, which partially depended on ZRANB2, SYF2 and the ECT2-Ex5+ isoform. Finally, doxorubicin combination with an oligonucleotide inhibiting ECT2-Ex5 inclusion reduced doxorubicin-resistant tumor growth in mouse xenografts, and high ECT2-Ex5 inclusion levels were associated with bad prognosis in breast cancer treated with chemotherapy. Altogether, our data identify AS programs controlled by ZRANB2 and SYF2 and converging on ECT2, that participate to breast cancer cell resistance to doxorubicin.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Alternative Splicing/drug effects ; Alternative Splicing/genetics ; Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Exons/genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Mice, Nude ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Middle Aged ; Protein Isoforms/metabolism ; Proto-Oncogene Proteins/metabolism ; RNA Splice Sites/genetics ; RNA-Binding Proteins/metabolism ; S Phase/drug effects ; Spliceosomes/metabolism
    Chemical Substances ECT2 protein, human ; GCIP-interacting protein p29, human ; MicroRNAs ; Protein Isoforms ; Proto-Oncogene Proteins ; RNA Splice Sites ; RNA-Binding Proteins ; ZRANB2 protein, human ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2020-01-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkz1213
    Database MEDical Literature Analysis and Retrieval System OnLINE

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