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  1. Article ; Online: The dawn of spatial omics.

    Bressan, Dario / Battistoni, Giorgia / Hannon, Gregory J

    Science (New York, N.Y.)

    2023  Volume 381, Issue 6657, Page(s) eabq4964

    Abstract: Spatial omics has been widely heralded as the new frontier in life sciences. This term encompasses a wide range of techniques that promise to transform many areas of biology and eventually revolutionize pathology by measuring physical tissue structure ... ...

    Abstract Spatial omics has been widely heralded as the new frontier in life sciences. This term encompasses a wide range of techniques that promise to transform many areas of biology and eventually revolutionize pathology by measuring physical tissue structure and molecular characteristics at the same time. Although the field came of age in the past 5 years, it still suffers from some growing pains: barriers to entry, robustness, unclear best practices for experimental design and analysis, and lack of standardization. In this Review, we present a systematic catalog of the different families of spatial omics technologies; highlight their principles, power, and limitations; and give some perspective and suggestions on the biggest challenges that lay ahead in this incredibly powerful-but still hard to navigate-landscape.
    MeSH term(s) Genomics/methods ; Research Design ; Humans ; Animals ; Mice ; Organ Specificity
    Language English
    Publishing date 2023-08-04
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.abq4964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: An evolutionarily conserved stop codon enrichment at the 5' ends of mammalian piRNAs.

    Bornelöv, Susanne / Czech, Benjamin / Hannon, Gregory J

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 2118

    Abstract: PIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5' ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically ... ...

    Abstract PIWI-interacting RNAs (piRNAs) are small RNAs required to recognize and silence transposable elements. The 5' ends of mature piRNAs are defined through cleavage of long precursor transcripts, primarily by Zucchini (Zuc). Zuc-dependent cleavage typically occurs immediately upstream of a uridine. However, Zuc lacks sequence preference in vitro, pointing towards additional unknown specificity factors. Here, we examine murine piRNAs and reveal a strong and specific enrichment of three sequences (UAA, UAG, UGA)-corresponding to stop codons-at piRNA 5' ends. Stop codon sequences are also enriched immediately after piRNA processing intermediates, reflecting their Zuc-dependent tail-to-head arrangement. Further analyses reveal that a Zuc in vivo cleavage preference at four sequences (UAA, UAG, UGA, UAC) promotes 5' end stop codons. This observation is conserved across mammals and possibly further. Our work provides new insights into Zuc-dependent cleavage and may point to a previously unrecognized connection between piRNA biogenesis and the translational machinery.
    MeSH term(s) Animals ; Codon, Terminator/genetics ; Drosophila Proteins/genetics ; Endoribonucleases/genetics ; Mammals/genetics ; Mice ; RNA, Small Interfering/genetics
    Chemical Substances Codon, Terminator ; Drosophila Proteins ; RNA, Small Interfering ; Endoribonucleases (EC 3.1.-)
    Language English
    Publishing date 2022-04-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29787-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mouse primordial germ-cell-like cells lack piRNAs.

    Ramakrishna, Navin B / Battistoni, Giorgia / Surani, M Azim / Hannon, Gregory J / Miska, Eric A

    Developmental cell

    2022  Volume 57, Issue 23, Page(s) 2661–2668.e5

    Abstract: PIWI-interacting RNAs (piRNAs) are small RNAs bound by PIWI-clade Argonaute proteins that function to silence transposable elements (TEs). Following mouse primordial germ cell (mPGC) specification around E6.25, fetal piRNAs emerge in male gonocytes from ... ...

    Abstract PIWI-interacting RNAs (piRNAs) are small RNAs bound by PIWI-clade Argonaute proteins that function to silence transposable elements (TEs). Following mouse primordial germ cell (mPGC) specification around E6.25, fetal piRNAs emerge in male gonocytes from E13.5 onward. The in vitro differentiation of mPGC-like cells (mPGCLCs) has raised the possibility of studying the fetal piRNA pathway in greater depth. However, using single-cell RNA-seq and RT-qPCR along mPGCLC differentiation, we find that piRNA pathway factors are not fully expressed in Day 6 mPGCLCs. Moreover, we do not detect piRNAs across a panel of Day 6 mPGCLC lines using small RNA-seq. Our combined efforts highlight that in vitro differentiated Day 6 mPGCLCs do not yet resemble E13.5 or later mouse gonocytes where the piRNA pathway is active. This Matters Arising paper is in response to von Meyenn et al. (2016), published in Developmental Cell. See also the correction by von Meyenn et al. published in this issue.
    MeSH term(s) Male ; Mice ; Animals ; Piwi-Interacting RNA ; Germ Cells
    Chemical Substances Piwi-Interacting RNA
    Language English
    Publishing date 2022-12-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2022.11.004
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  4. Article ; Online: lncRNAs in development and disease: from functions to mechanisms.

    Delás, M Joaquina / Hannon, Gregory J

    Open biology

    2017  Volume 7, Issue 7

    Abstract: Differential expression of long non-coding RNAs (lncRNAs) during differentiation and their misregulation in cancer highlight their potential as cell fate regulators. While some example lncRNAs have been characterized in great detail, the ... ...

    Abstract Differential expression of long non-coding RNAs (lncRNAs) during differentiation and their misregulation in cancer highlight their potential as cell fate regulators. While some example lncRNAs have been characterized in great detail, the functional
    MeSH term(s) Animals ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Chromatin/genetics ; Chromatin/metabolism ; Gene Expression Regulation, Developmental ; Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Neoplasms/genetics ; Neoplasms/metabolism ; Organ Specificity/genetics ; RNA, Long Noncoding/genetics
    Chemical Substances Chromatin ; RNA, Long Noncoding
    Language English
    Publishing date 2017-07-25
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2630944-0
    ISSN 2046-2441 ; 2046-2441
    ISSN (online) 2046-2441
    ISSN 2046-2441
    DOI 10.1098/rsob.170121
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  5. Article ; Online: Unistrand piRNA clusters are an evolutionarily conserved mechanism to suppress endogenous retroviruses across the Drosophila genus.

    van Lopik, Jasper / Alizada, Azad / Trapotsi, Maria-Anna / Hannon, Gregory J / Bornelöv, Susanne / Czech Nicholson, Benjamin

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 7337

    Abstract: The PIWI-interacting RNA (piRNA) pathway prevents endogenous genomic parasites, i.e. transposable elements, from damaging the genetic material of animal gonadal cells. Specific regions in the genome, called piRNA clusters, are thought to define each ... ...

    Abstract The PIWI-interacting RNA (piRNA) pathway prevents endogenous genomic parasites, i.e. transposable elements, from damaging the genetic material of animal gonadal cells. Specific regions in the genome, called piRNA clusters, are thought to define each species' piRNA repertoire and therefore its capacity to recognize and silence specific transposon families. The unistrand cluster flamenco (flam) is essential in the somatic compartment of the Drosophila ovary to restrict Gypsy-family transposons from infecting the neighbouring germ cells. Disruption of flam results in transposon de-repression and sterility, yet it remains unknown whether this silencing mechanism is present more widely. Here, we systematically characterise 119 Drosophila species and identify five additional flam-like clusters separated by up to 45 million years of evolution. Small RNA-sequencing validated these as bona-fide unistrand piRNA clusters expressed in somatic cells of the ovary, where they selectively target transposons of the Gypsy family. Together, our study provides compelling evidence of a widely conserved transposon silencing mechanism that co-evolved with virus-like Gypsy-family transposons.
    MeSH term(s) Humans ; Animals ; Female ; Drosophila/genetics ; Drosophila/metabolism ; Piwi-Interacting RNA ; Endogenous Retroviruses/genetics ; Endogenous Retroviruses/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; DNA Transposable Elements/genetics ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism
    Chemical Substances Piwi-Interacting RNA ; Drosophila Proteins ; RNA, Small Interfering ; Argonaute Proteins ; DNA Transposable Elements
    Language English
    Publishing date 2023-11-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-42787-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A Happy 3' Ending to the piRNA Maturation Story.

    Czech, Benjamin / Hannon, Gregory J

    Cell

    2016  Volume 164, Issue 5, Page(s) 838–840

    Abstract: For a decade, mystery has surrounded the mechanisms by which piRNA biogenesis yields distinct size classes of small RNAs within individual PIWI proteins. In this issue of Cell, two studies shed light on this process, identifying conserved PARN-family ... ...

    Abstract For a decade, mystery has surrounded the mechanisms by which piRNA biogenesis yields distinct size classes of small RNAs within individual PIWI proteins. In this issue of Cell, two studies shed light on this process, identifying conserved PARN-family exonucleases that trim piRNAs to their mature size in silkworms and C. elegans.
    Language English
    Publishing date 2016-02-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2016.02.012
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  7. Article ; Online: Inducing RNAi in Caenorhabditis elegans by Injection of dsRNA.

    Hammell, Christopher M / Hannon, Gregory J

    Cold Spring Harbor protocols

    2016  Volume 2016, Issue 1, Page(s) pdb.prot086306

    Abstract: In Caenorhabditis elegans, long double-stranded RNAs (dsRNAs) are overwhelmingly the trigger of choice for inducing RNA interference (RNAi). Although injection of dsRNA into the somatic or germline tissues of animals requires both specific equipment and ... ...

    Abstract In Caenorhabditis elegans, long double-stranded RNAs (dsRNAs) are overwhelmingly the trigger of choice for inducing RNA interference (RNAi). Although injection of dsRNA into the somatic or germline tissues of animals requires both specific equipment and technical skills, the ability of C. elegans to amplify the initial dsRNA trigger and to transmit the RNAi activity to other somatic tissues and to the progeny of injected animals is one of the main advantages of using C. elegans as a model system. The direct injection of dsRNA into parental animals is the most reliable method for RNAi and also presents the least experiment-to-experiment and animal-to-animal variability.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Microinjections ; RNA Interference/physiology ; RNA, Double-Stranded/administration & dosage ; RNA, Double-Stranded/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; RNA, Double-Stranded
    Language English
    Publishing date 2016-01-04
    Publishing country United States
    Document type Journal Article
    ISSN 1559-6095
    ISSN (online) 1559-6095
    DOI 10.1101/pdb.prot086306
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  8. Article: One Loop to Rule Them All: The Ping-Pong Cycle and piRNA-Guided Silencing.

    Czech, Benjamin / Hannon, Gregory J

    Trends in biochemical sciences

    2016  Volume 41, Issue 4, Page(s) 324–337

    Abstract: The PIWI-interacting RNA (piRNA) pathway is a conserved defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites, such as transposons. Discovered nearly a decade ago, this small RNA ... ...

    Abstract The PIWI-interacting RNA (piRNA) pathway is a conserved defense mechanism that protects the genetic information of animal germ cells from the deleterious effects of molecular parasites, such as transposons. Discovered nearly a decade ago, this small RNA silencing system comprises PIWI-clade Argonaute proteins and their associated RNA-binding partners, the piRNAs. In this review, we highlight recent work that has advanced our understanding of how piRNAs preserve genome integrity across generations. We discuss the mechanism of piRNA biogenesis, give an overview of common themes as well as differences in piRNA-mediated silencing between species, and end by highlighting known and emerging functions of piRNAs.
    MeSH term(s) Animals ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Gene Silencing ; Histones/genetics ; Histones/metabolism ; Humans ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Transcription, Genetic
    Chemical Substances Argonaute Proteins ; Chromosomal Proteins, Non-Histone ; Cuff protein, Drosophila ; Drosophila Proteins ; Histones ; Microtubule-Associated Proteins ; RNA, Messenger ; RNA, Small Interfering ; RNA-Binding Proteins ; del protein, Drosophila ; rhi protein, Drosophila
    Language English
    Publishing date 2016-01-19
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2015.12.008
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  9. Article ; Online: Maternally inherited piRNAs direct transient heterochromatin formation at active transposons during early

    Fabry, Martin H / Falconio, Federica A / Joud, Fadwa / Lythgoe, Emily K / Czech, Benjamin / Hannon, Gregory J

    eLife

    2021  Volume 10

    Abstract: The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. ... ...

    Abstract The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. In
    MeSH term(s) Animals ; Chromatin ; DNA Transposable Elements ; Developmental Biology ; Drosophila/embryology ; Drosophila/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/physiology ; Embryonic Development/genetics ; Embryonic Development/physiology ; Epigenomics ; Female ; Gene Expression ; Germ Cells/metabolism ; Heterochromatin/metabolism ; Histones/metabolism ; Male ; Maternal Inheritance/genetics ; Maternal Inheritance/physiology ; RNA, Small Interfering/metabolism
    Chemical Substances Chromatin ; DNA Transposable Elements ; Drosophila Proteins ; Heterochromatin ; Histones ; RNA, Small Interfering
    Language English
    Publishing date 2021-07-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.68573
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  10. Article ; Online: Clonal transcriptomics identifies mechanisms of chemoresistance and empowers rational design of combination therapies.

    Wild, Sophia A / Cannell, Ian G / Nicholls, Ashley / Kania, Katarzyna / Bressan, Dario / Hannon, Gregory J / Sawicka, Kirsty

    eLife

    2022  Volume 11

    Abstract: Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained ... ...

    Abstract Tumour heterogeneity is thought to be a major barrier to successful cancer treatment due to the presence of drug resistant clonal lineages. However, identifying the characteristics of such lineages that underpin resistance to therapy has remained challenging. Here, we utilise clonal transcriptomics with WILD-seq;
    MeSH term(s) Humans ; Mice ; Animals ; Drug Resistance, Neoplasm/genetics ; Nuclear Proteins ; Transcriptome ; Asparagine ; Transcription Factors ; Triple Negative Breast Neoplasms/pathology ; Taxoids/pharmacology ; Taxoids/therapeutic use
    Chemical Substances Nuclear Proteins ; Asparagine (7006-34-0) ; Transcription Factors ; taxane (1605-68-1) ; Taxoids
    Language English
    Publishing date 2022-12-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.80981
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