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  1. Article ; Online: RNA circuits and RNA-binding proteins in T cells.

    Zhu, Wandi S / Wheeler, Benjamin D / Ansel, K Mark

    Trends in immunology

    2023  Volume 44, Issue 10, Page(s) 792–806

    Abstract: RNA is integral to the regulatory circuits that control cell identity and behavior. Cis-regulatory elements in mRNAs interact with RNA-binding proteins (RBPs) that can alter RNA sequence, stability, and translation into protein. Similarly, long noncoding ...

    Abstract RNA is integral to the regulatory circuits that control cell identity and behavior. Cis-regulatory elements in mRNAs interact with RNA-binding proteins (RBPs) that can alter RNA sequence, stability, and translation into protein. Similarly, long noncoding RNAs (lncRNAs) scaffold ribonucleoprotein complexes that mediate transcriptional and post-transcriptional regulation of gene expression. Indeed, cell programming is fundamental to multicellular life and, in this era of cellular therapies, it is of particular interest in T cells. Here, we review key concepts and recent advances in our understanding of the RNA circuits and RBPs that govern mammalian T cell differentiation and immune function.
    MeSH term(s) Animals ; Humans ; RNA ; T-Lymphocytes/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Ribonucleoproteins ; RNA, Messenger/metabolism ; RNA, Long Noncoding/genetics ; Mammals
    Chemical Substances RNA (63231-63-0) ; RNA-Binding Proteins ; Ribonucleoproteins ; RNA, Messenger ; RNA, Long Noncoding
    Language English
    Publishing date 2023-08-18
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2023.07.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The lncRNA

    Wheeler, Benjamin D / Gagnon, John D / Zhu, Wandi S / Muñoz-Sandoval, Priscila / Wong, Simon K / Simeonov, Dimitre S / Li, Zhongmei / DeBarge, Rachel / Spitzer, Matthew H / Marson, Alexander / Ansel, K Mark

    eLife

    2023  Volume 12

    Abstract: Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, intracellular bacteria, and cancers. Through biochemical analysis of RNA:protein interactions, we ... ...

    Abstract Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, intracellular bacteria, and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA
    MeSH term(s) Animals ; Mice ; CD28 Antigens ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics ; T-Lymphocytes, Cytotoxic ; Memory T Cells
    Chemical Substances CD28 Antigens ; MicroRNAs ; RNA, Long Noncoding ; Malat1 long non-coding RNA, mouse ; Mirn15 microRNA, mouse ; Mirn16 microRNA, mouse
    Language English
    Publishing date 2023-12-21
    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.87900
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: The lncRNA Malat1 Inhibits miR-15/16 to Enhance Cytotoxic T Cell Activation and Memory Cell Formation.

    Wheeler, Benjamin D / Gagnon, John D / Zhu, Wandi S / Muñoz-Sandoval, Priscila / Wong, Simon K / Simeonov, Dimitre R / Li, Zhongmei / Debarge, Rachel / Spitzer, Matthew H / Marson, Alexander / Ansel, K Mark

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, many intracellular bacteria and cancers. Through biochemical analysis of RNA:protein interactions, we ... ...

    Abstract Proper activation of cytotoxic T cells via the T cell receptor and the costimulatory receptor CD28 is essential for adaptive immunity against viruses, many intracellular bacteria and cancers. Through biochemical analysis of RNA:protein interactions, we uncovered a non-coding RNA circuit regulating activation and differentiation of cytotoxic T cells composed of the long non-coding RNA Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and the microRNA family miR-15/16. miR-15/16 is a widely and highly expressed tumor suppressor miRNA family important for cell proliferation and survival. miR-15/16 also play important roles in T cell responses to viral infection, including the regulation of antigen-specific T cell expansion and T cell memory. Comparative Argonaute-2 high throughput sequencing of crosslinking immunoprecipitation (Ago2 HITS-CLIP, or AHC) combined with gene expression profiling in normal and miR-15/16-deficient T cells revealed a large network of several hundred direct miR-15/16 target mRNAs, many with functional relevance for T cell activation, survival and memory formation. Among these targets, the long non-coding RNA Malat1 contained the largest absolute magnitude miR-15/16-dependent AHC peak in T cells. This binding site was also among the strongest lncRNA:miRNA interactions detected in the T cell transcriptome. We used CRISPR targeting with homology directed repair to generate mice with a 5-nucleotide mutation in the miR-15/16 binding site in Malat1. This mutation interrupted Malat1:miR-15/16 interaction, and enhanced the repression of other miR-15/16 target genes, including CD28. Interrupting Malat1 interaction with miR-15/16 decreased cytotoxic T cell activation, including the expression of IL-2 and a broader CD28-responsive gene program. Accordingly, Malat1 mutation diminished memory cell persistence following LCMV Armstrong and
    Language English
    Publishing date 2023-07-29
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.04.14.536843
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A Mass Spectrometric Assay of METTL3/METTL14 Methyltransferase Activity.

    Buker, Shane M / Gurard-Levin, Zachary A / Wheeler, Benjamin D / Scholle, Michael D / Case, April W / Hirsch, Jeffrey L / Ribich, Scott / Copeland, Robert A / Boriack-Sjodin, P Ann

    SLAS discovery : advancing life sciences R & D

    2019  Volume 25, Issue 4, Page(s) 361–371

    Abstract: A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA processing, stability, and translation. Methylation of adenosine at the N6 position ( ... ...

    Abstract A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA processing, stability, and translation. Methylation of adenosine at the N6 position (m
    MeSH term(s) Adenosine/analogs & derivatives ; Adenosine/genetics ; Adenosine/pharmacology ; Drug Discovery/trends ; Gene Expression Regulation, Developmental/drug effects ; Humans ; Mass Spectrometry/methods ; Methylation/drug effects ; Methyltransferases/genetics ; Multiprotein Complexes/antagonists & inhibitors ; Multiprotein Complexes/genetics ; RNA Processing, Post-Transcriptional/drug effects ; RNA Processing, Post-Transcriptional/genetics ; RNA Stability/drug effects ; RNA Stability/genetics ; RNA, Messenger/drug effects ; RNA, Messenger/genetics ; S-Adenosylhomocysteine/pharmacology
    Chemical Substances Multiprotein Complexes ; RNA, Messenger ; S-Adenosylhomocysteine (979-92-0) ; METTL14 protein, human (EC 2.1.1.-) ; Methyltransferases (EC 2.1.1.-) ; METTL3 protein, human (EC 2.1.1.62) ; Adenosine (K72T3FS567) ; sinefungin (W2U467CIIL)
    Language English
    Publishing date 2019-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2885123-7
    ISSN 2472-5560 ; 2472-5552
    ISSN (online) 2472-5560
    ISSN 2472-5552
    DOI 10.1177/2472555219878408
    Database MEDical Literature Analysis and Retrieval System OnLINE

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