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  1. Article: The role of RNA-binding proteins in orchestrating germline development in

    Albarqi, Mennatallah M Y / Ryder, Sean P

    Frontiers in cell and developmental biology

    2023  Volume 10, Page(s) 1094295

    Abstract: RNA passed from parents to progeny controls several aspects of early development. The germline of the free-living ... ...

    Abstract RNA passed from parents to progeny controls several aspects of early development. The germline of the free-living nematode
    Language English
    Publishing date 2023-01-04
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.1094295
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: #CRISPRbabies: Notes on a Scandal.

    Ryder, Sean P

    The CRISPR journal

    2018  Volume 1, Issue 6, Page(s) 355–357

    Language English
    Publishing date 2018-12-20
    Publishing country United States
    Document type Journal Article
    ISSN 2573-1599
    ISSN 2573-1599
    DOI 10.1089/crispr.2018.29039.spr
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  3. Article ; Online: Analysis of Rapidly Emerging Variants in Structured Regions of the SARS-CoV-2 Genome

    Ryder, Sean P.

    bioRxiv

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around that globe. They also provide a unique opportunity to observe virus evolution in real time. Here, I evaluate two cohorts of SARS-CoV-2 genomic sequences to identify rapidly emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, twenty variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5’UTR, including a set of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-stable molecular switch in the 3’UTR. Finally, five variants destabilize structured elements within the 3’UTR hypervariable region, including the S2M stem loop, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. This analysis has implications for the development therapeutics that target viral cis-regulatory RNA structures or sequences, as rapidly emerging variations in these regions could lead to drug resistance.
    Keywords covid19
    Publisher BioRxiv
    Document type Article ; Online
    DOI 10.1101/2020.05.27.120105
    Database COVID19

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  4. Book ; Online: Analysis of Rapidly Emerging Variants in Structured Regions of the SARS-CoV-2 Genome

    Ryder, Sean P.

    COVID-19 Publications by UMMS Authors

    2020  

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around that globe. They also provide a unique opportunity to observe virus evolution in real time. Here, I evaluate two cohorts of SARS-CoV-2 genomic sequences to identify rapidly emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, twenty variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5’UTR, including a set of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-stable molecular switch in the 3’UTR. Finally, five variants destabilize structured elements within the 3’UTR hypervariable region, including the S2M stem loop, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. This analysis has implications for the development therapeutics that target viral cis-regulatory RNA structures or sequences, as rapidly emerging variations in these regions could lead to drug resistance.
    Keywords SARS ; COVID-19 ; RNA Structure ; Coronavirus ; Phylogeny ; Bioinformatics ; Computational Biology ; Genomics ; Immunology and Infectious Disease ; Infectious Disease ; Nucleic Acids ; Nucleotides ; and Nucleosides ; Structural Biology ; Virology ; Virus Diseases ; covid19
    Subject code 572
    Publishing date 2020-05-28T07:00:00Z
    Publisher eScholarship@UMMS
    Publishing country us
    Document type Book ; Online
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  5. Article ; Online: Personal reflection (RNA journal 20th anniversary).

    Ryder, Sean P

    RNA (New York, N.Y.)

    2015  Volume 21, Issue 4, Page(s) 725–726

    MeSH term(s) Publishing ; RNA
    Chemical Substances RNA (63231-63-0)
    Language English
    Publishing date 2015-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1241540-6
    ISSN 1469-9001 ; 1355-8382
    ISSN (online) 1469-9001
    ISSN 1355-8382
    DOI 10.1261/rna.050005.115
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    In stock of ZB MED Cologne/Königswinter

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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
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  6. Article: Protein-mRNA interactome capture: cartography of the mRNP landscape.

    Ryder, Sean P

    F1000Research

    2016  Volume 5, Page(s) 2627

    Abstract: RNA-binding proteins play a variety of roles in cellular physiology. Some regulate mRNA processing, mRNA abundance, and translation efficiency. Some fight off invader RNA through small RNA-driven silencing pathways. Others sense foreign sequences in the ... ...

    Abstract RNA-binding proteins play a variety of roles in cellular physiology. Some regulate mRNA processing, mRNA abundance, and translation efficiency. Some fight off invader RNA through small RNA-driven silencing pathways. Others sense foreign sequences in the form of double-stranded RNA and activate the innate immune response. Yet others, for example cytoplasmic aconitase, act as bi-functional proteins, processing metabolites in one conformation and regulating metabolic gene expression in another. Not all are involved in gene regulation. Some play structural roles, for example, connecting the translational machinery to the endoplasmic reticulum outer membrane. Despite their pervasive role and relative importance, it has remained difficult to identify new RNA-binding proteins in a systematic, unbiased way. A recent body of literature from several independent labs has defined robust, easily adaptable protocols for mRNA interactome discovery. In this review, I summarize the methods and review some of the intriguing findings from their application to a wide variety of biological systems.
    Language English
    Publishing date 2016-11-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2699932-8
    ISSN 2046-1402
    ISSN 2046-1402
    DOI 10.12688/f1000research.9404.1
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  7. Article ; Online: A nematode model to evaluate microdeletion phenotype expression.

    Antkowiak, Katianna R / Coskun, Peren / Noronha, Sharon T / Tavella, Davide / Massi, Francesca / Ryder, Sean P

    G3 (Bethesda, Md.)

    2023  Volume 14, Issue 2

    Abstract: Microdeletion syndromes are genetic diseases caused by multilocus chromosomal deletions too small to be detected by karyotyping. They are typified by complex pleiotropic developmental phenotypes that depend both on the extent of the deletion and ... ...

    Abstract Microdeletion syndromes are genetic diseases caused by multilocus chromosomal deletions too small to be detected by karyotyping. They are typified by complex pleiotropic developmental phenotypes that depend both on the extent of the deletion and variations in genetic background. Microdeletion alleles cause a wide array of consequences involving multiple pathways. How simultaneous haploinsufficiency of numerous adjacent genes leads to complex and variable pleiotropic phenotypes is not well understood. CRISPR/Cas9 genome editing has been shown to induce microdeletion-like alleles at a meaningful rate. Here, we describe a microdeletion allele in Caenorhabditis elegans recovered during a CRISPR/Cas9 genome editing experiment. We mapped the allele to chromosome V, balanced it with a reciprocal translocation crossover suppressor, and precisely defined the breakpoint junction. The allele simultaneously removes 32 protein-coding genes, yet animals homozygous for this mutation are viable as adults. Homozygous animals display a complex phenotype including maternal effect lethality, producing polynucleated embryos that grow into uterine tumors, vulva morphogenesis defects, body wall distensions, uncoordinated movement, and a shortened life span typified by death by bursting. Our work provides an opportunity to explore the complexity and penetrance of microdeletion phenotypes in a simple genetic model system.
    MeSH term(s) Animals ; Female ; Phenotype ; Gene Editing ; Mutation ; Caenorhabditis elegans/genetics ; Chromosome Deletion
    Language English
    Publishing date 2023-11-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2629978-1
    ISSN 2160-1836 ; 2160-1836
    ISSN (online) 2160-1836
    ISSN 2160-1836
    DOI 10.1093/g3journal/jkad258
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  8. Article ; Online: The endogenous mex-3 3´UTR is required for germline repression and contributes to optimal fecundity in C. elegans.

    Albarqi, Mennatallah M Y / Ryder, Sean P

    PLoS genetics

    2021  Volume 17, Issue 8, Page(s) e1009775

    Abstract: RNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, regulating the translation and stability of ... ...

    Abstract RNA regulation is essential to successful reproduction. Messenger RNAs delivered from parent to progeny govern early embryonic development. RNA-binding proteins (RBPs) are the key effectors of this process, regulating the translation and stability of parental transcripts to control cell fate specification events prior to zygotic gene activation. The KH-domain RBP MEX-3 is conserved from nematode to human. It was first discovered in Caenorhabditis elegans, where it is essential for anterior cell fate and embryo viability. Here, we show that loss of the endogenous mex-3 3´UTR disrupts its germline expression pattern. An allelic series of 3´UTR deletion variants identify repressing regions of the UTR and demonstrate that repression is not precisely coupled to reproductive success. We also show that several RBPs regulate mex-3 mRNA through its 3´UTR to define its unique germline spatiotemporal expression pattern. Additionally, we find that both poly(A) tail length control and the translation initiation factor IFE-3 contribute to its expression pattern. Together, our results establish the importance of the mex-3 3´UTR to reproductive health and its expression in the germline. Our results suggest that additional mechanisms control MEX-3 function when 3´UTR regulation is compromised.
    MeSH term(s) 3' Untranslated Regions/genetics ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Embryonic Development/genetics ; Fertility/genetics ; Gene Expression Regulation, Developmental/genetics ; Germ Cells/metabolism ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism
    Chemical Substances 3' Untranslated Regions ; Caenorhabditis elegans Proteins ; MEX-3 protein, C elegans ; RNA, Messenger ; RNA-Binding Proteins
    Language English
    Publishing date 2021-08-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1009775
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  9. Article: Analysis of Rapidly Emerging Variants in Structured Regions of the SARS-CoV-2 Genome.

    Ryder, Sean P / Morgan, Brittany R / Massi, Francesca

    bioRxiv : the preprint server for biology

    2020  

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has motivated a widespread effort to understand its epidemiology and pathogenic mechanisms. Modern high-throughput sequencing technology has led to the deposition of vast numbers of SARS-CoV-2 genome sequences in curated repositories, which have been useful in mapping the spread of the virus around the globe. They also provide a unique opportunity to observe virus evolution in real time. Here, we evaluate two cohorts of SARS-CoV-2 genomic sequences to identify rapidly emerging variants within structured cis-regulatory elements of the SARS-CoV-2 genome. Overall, twenty variants are present at a minor allele frequency of at least 0.5%. Several enhance the stability of Stem Loop 1 in the 5'UTR, including a set of co-occurring variants that extend its length. One appears to modulate the stability of the frameshifting pseudoknot between ORF1a and ORF1b, and another perturbs a bi-stable molecular switch in the 3'UTR. Finally, five variants destabilize structured elements within the 3'UTR hypervariable region, including the S2M stem loop, raising questions as to the functional relevance of these structures in viral replication. Two of the most abundant variants appear to be caused by RNA editing, suggesting host-viral defense contributes to SARS-CoV-2 genome heterogeneity. This analysis has implications for the development of therapeutics that target viral cis-regulatory RNA structures or sequences, as rapidly emerging variations in these regions could lead to drug resistance.
    Keywords covid19
    Language English
    Publishing date 2020-06-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.05.27.120105
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  10. Article ; Online: Protein-mRNA interactome capture

    Sean P. Ryder

    F1000Research, Vol

    cartography of the mRNP landscape [version 1; referees: 3 approved]

    2016  Volume 5

    Abstract: RNA-binding proteins play a variety of roles in cellular physiology. Some regulate mRNA processing, mRNA abundance, and translation efficiency. Some fight off invader RNA through small RNA-driven silencing pathways. Others sense foreign sequences in the ... ...

    Abstract RNA-binding proteins play a variety of roles in cellular physiology. Some regulate mRNA processing, mRNA abundance, and translation efficiency. Some fight off invader RNA through small RNA-driven silencing pathways. Others sense foreign sequences in the form of double-stranded RNA and activate the innate immune response. Yet others, for example cytoplasmic aconitase, act as bi-functional proteins, processing metabolites in one conformation and regulating metabolic gene expression in another. Not all are involved in gene regulation. Some play structural roles, for example, connecting the translational machinery to the endoplasmic reticulum outer membrane. Despite their pervasive role and relative importance, it has remained difficult to identify new RNA-binding proteins in a systematic, unbiased way. A recent body of literature from several independent labs has defined robust, easily adaptable protocols for mRNA interactome discovery. In this review, I summarize the methods and review some of the intriguing findings from their application to a wide variety of biological systems.
    Keywords Control of Gene Expression ; Developmental Molecular Mechanisms ; Medical Microbiology ; Parasitology ; Protein Chemistry & Proteomics ; Structure: RNA ; Medicine ; R ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2016-11-01T00:00:00Z
    Publisher F1000 Research Ltd
    Document type Article ; Online
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