LIVIVO - Search results -

Search results

Result 1 - 10 of total 71

Search options

Article: 3' RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease.

Menezes, Miriam R / Balzeau, Julien / Hagan, John P

2018 Volume 5, Page(s) 61

Abstract: Emerging evidence implicates a wide range of post-transcriptional RNA modifications that play crucial roles in fundamental biological processes including regulating gene expression. Collectively, they are known as epitranscriptomics. Recent studies ... ...

Abstract	Emerging evidence implicates a wide range of post-transcriptional RNA modifications that play crucial roles in fundamental biological processes including regulating gene expression. Collectively, they are known as epitranscriptomics. Recent studies implicate 3' RNA uridylation, the non-templated addition of uridine(s) to the terminal end of RNA, as a key player in epitranscriptomics. In this review, we describe the functional roles and significance of 3' terminal RNA uridylation that has diverse functions in regulating both mRNAs and non-coding RNAs. In mammals, three Terminal Uridylyl Transferases (TUTases) are primarily responsible for 3' RNA uridylation. These enzymes are also referred to as polyU polymerases. TUTase 1 (TUT1) is implicated in U6 snRNA maturation via uridylation. The TUTases TUT4 and/or TUT7 are the predominant mediators of all other cellular uridylation. Terminal uridylation promotes turnover for many polyadenylated mRNAs, replication-dependent histone mRNAs that lack polyA-tails, and aberrant structured noncoding RNAs. In addition, uridylation regulates biogenesis of a subset of microRNAs and generates isomiRs, sequent variant microRNAs that have altered function in specific cases. For example, the RNA binding protein and proto-oncogene LIN28A and TUT4 work together to polyuridylate pre-let-7, thereby blocking biogenesis and function of the tumor suppressor let-7 microRNA family. In contrast, monouridylation of Group II pre-miRNAs creates an optimal 3' overhang that promotes recognition and subsequent cleavage by the Dicer-TRBP complex that then yields the mature microRNA. Also, uridylation may play a role in non-canonical microRNA biogenesis. The overall significance of 3' RNA uridylation is discussed with an emphasis on mammalian development, gene regulation, and disease, including cancer and Perlman syndrome. We also introduce recent changes to the HUGO-approved gene names for multiple terminal nucleotidyl transferases that affects in part TUTase nomenclature (TUT1/TENT1, TENT2/PAPD4/GLD2, TUT4/ZCCHC11/TENT3A, TUT7/ZCCHC6/TENT3B, TENT4A/PAPD7, TENT4B/PAPD5, TENT5A/FAM46A, TENT5B/FAM46B, TENT5C/FAM46C, TENT5D/FAM46D, MTPAP/TENT6/PAPD1).
Language	English
Publishing date	2018-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2018.00061
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: 3′ RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease

Miriam R. Menezes / Julien Balzeau / John P. Hagan

Frontiers in Molecular Biosciences, Vol

2018 Volume 5

Abstract	Emerging evidence implicates a wide range of post-transcriptional RNA modifications that play crucial roles in fundamental biological processes including regulating gene expression. Collectively, they are known as epitranscriptomics. Recent studies implicate 3′ RNA uridylation, the non-templated addition of uridine(s) to the terminal end of RNA, as a key player in epitranscriptomics. In this review, we describe the functional roles and significance of 3′ terminal RNA uridylation that has diverse functions in regulating both mRNAs and non-coding RNAs. In mammals, three Terminal Uridylyl Transferases (TUTases) are primarily responsible for 3′ RNA uridylation. These enzymes are also referred to as polyU polymerases. TUTase 1 (TUT1) is implicated in U6 snRNA maturation via uridylation. The TUTases TUT4 and/or TUT7 are the predominant mediators of all other cellular uridylation. Terminal uridylation promotes turnover for many polyadenylated mRNAs, replication-dependent histone mRNAs that lack polyA-tails, and aberrant structured noncoding RNAs. In addition, uridylation regulates biogenesis of a subset of microRNAs and generates isomiRs, sequent variant microRNAs that have altered function in specific cases. For example, the RNA binding protein and proto-oncogene LIN28A and TUT4 work together to polyuridylate pre-let-7, thereby blocking biogenesis and function of the tumor suppressor let-7 microRNA family. In contrast, monouridylation of Group II pre-miRNAs creates an optimal 3′ overhang that promotes recognition and subsequent cleavage by the Dicer-TRBP complex that then yields the mature microRNA. Also, uridylation may play a role in non-canonical microRNA biogenesis. The overall significance of 3′ RNA uridylation is discussed with an emphasis on mammalian development, gene regulation, and disease, including cancer and Perlman syndrome. We also introduce recent changes to the HUGO-approved gene names for multiple terminal nucleotidyl transferases that affects in part TUTase nomenclature (TUT1/TENT1, ...
Keywords	RNA epitranscritpomics ; 3′ terminal RNA uridylation ; TUTase ; LIN28/let-7 pathway ; DIS3L2 ; cancer ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: The LIN28/let-7 Pathway in Cancer.

Balzeau, Julien / Menezes, Miriam R / Cao, Siyu / Hagan, John P

Frontiers in genetics

2017 Volume 8, Page(s) 31

Abstract: Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is ... ...

Abstract	Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function. For LIN28B, the precise mechanism responsible for let-7 inhibition remains controversial. Functionally, the decrease in let-7 microRNAs leads to overexpression of their oncogenic targets such as MYC, RAS, HMGA2, BLIMP1, among others. Furthermore, mouse models demonstrate that ectopic LIN28 expression is sufficient to drive and/or accelerate tumorigenesis via a let-7 dependent mechanism. In this review, the LIN28/let-7 pathway is discussed, emphasizing its role in tumorigenesis, cancer stem cell biology, metabolomics, metastasis, and resistance to ionizing radiation and several chemotherapies. Also, emerging evidence will be presented suggesting that molecular targeting of this pathway may provide therapeutic benefit in cancer.
Language	English
Publishing date	2017-03-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2017.00031
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Mouse models of DNA polymerases.

Menezes, Miriam R / Sweasy, Joann B

Environmental and molecular mutagenesis

2012 Volume 53, Issue 9, Page(s) 645–665

Abstract: In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this contribution, which included the isolation and characterization of Escherichia coli DNA ... ...

Abstract	In 1956, Arthur Kornberg discovered the mechanism of the biological synthesis of DNA and was awarded the Nobel Prize in Physiology or Medicine in 1959 for this contribution, which included the isolation and characterization of Escherichia coli DNA polymerase I. Now there are 15 known DNA polymerases in mammalian cells that belong to four different families. These DNA polymerases function in many different cellular processes including DNA replication, DNA repair, and damage tolerance. Several biochemical and cell biological studies have provoked a further investigation of DNA polymerase function using mouse models in which polymerase genes have been altered using gene-targeting techniques. The phenotypes of mice harboring mutant alleles reveal the prominent role of DNA polymerases in embryogenesis, prevention of premature aging, and cancer suppression.
MeSH term(s)	Alleles ; Animals ; DNA Damage ; DNA Repair ; DNA-Directed DNA Polymerase/genetics ; DNA-Directed DNA Polymerase/physiology ; Mice ; Models, Animal ; Mutation ; Recombination, Genetic
Chemical Substances	DNA-Directed DNA Polymerase (EC 2.7.7.7)
Language	English
Publishing date	2012-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	639145-x
ISSN	1098-2280 ; 0893-6692
ISSN (online)	1098-2280
ISSN	0893-6692
DOI	10.1002/em.21731
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.B 2404: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Measuring deaminated nucleotide surveillance enzyme ITPA activity with an ATP-releasing nucleotide chimera.

Ji, Debin / Stepchenkova, Elena I / Cui, Jian / Menezes, Miriam R / Pavlov, Youri I / Kool, Eric T

Nucleic acids research

2017 Volume 45, Issue 20, Page(s) 11515–11524

Abstract: Nucleotide quality surveillance enzymes play important roles in human health, by detecting damaged molecules in the nucleotide pool and deactivating them before they are incorporated into chromosomal DNA or adversely affect metabolism. In particular, ... ...

Abstract	Nucleotide quality surveillance enzymes play important roles in human health, by detecting damaged molecules in the nucleotide pool and deactivating them before they are incorporated into chromosomal DNA or adversely affect metabolism. In particular, deamination of adenine moiety in (deoxy)nucleoside triphosphates, resulting in formation of (d)ITP, can be deleterious, leading to DNA damage, mutagenesis and other harmful cellular effects. The 21.5 kDa human enzyme that mitigates this damage by conversion of (d)ITP to monophosphate, ITPA, has been proposed as a possible therapeutic and diagnostic target for multiple diseases. Measuring the activity of this enzyme is useful both in basic research and in clinical applications involving this pathway, but current methods are nonselective and are not applicable to measurement of the enzyme from cells or tissues. Here, we describe the design and synthesis of an ITPA-specific chimeric dinucleotide (DIAL) that replaces the pyrophosphate leaving group of the native substrate with adenosine triphosphate, enabling sensitive detection via luciferase luminescence signaling. The probe is shown to function sensitively and selectively to quantify enzyme activity in vitro, and can be used to measure the activity of ITPA in bacterial, yeast and human cell lysates.
MeSH term(s)	Adenosine Triphosphate/chemistry ; Cell Extracts/chemistry ; Cell Line, Tumor ; DNA/genetics ; DNA Damage/genetics ; Deamination ; Enzyme Assays/methods ; Fluorescent Dyes/chemistry ; HeLa Cells ; Humans ; Inosine Monophosphate/analogs & derivatives ; Inosine Monophosphate/chemistry ; Luminescent Measurements/methods ; Pyrophosphatases/genetics ; Pyrophosphatases/metabolism ; RNA Interference ; RNA, Small Interfering/genetics
Chemical Substances	Cell Extracts ; Fluorescent Dyes ; RNA, Small Interfering ; Inosine Monophosphate (131-99-7) ; deoxyinosine monophosphate (3393-18-8) ; Adenosine Triphosphate (8L70Q75FXE) ; DNA (9007-49-2) ; Pyrophosphatases (EC 3.6.1.-) ; ITPA protein, human (EC 3.6.1.9)
Language	English
Publishing date	2017-10-04
Publishing country	England
Document type	Journal Article
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/gkx774
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1067: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Highly efficient one-step scarless protein tagging by type IIS restriction endonuclease-mediated precision cloning.

Xu, Zhen / Rui, Yan-Ning / Balzeau, Julien / Menezes, Miriam R / Niu, Airu / Hagan, John P / Kim, Dong H

Biochemical and biophysical research communications

2017 Volume 490, Issue 1, Page(s) 8–16

Abstract: Protein tagging with a wide variety of epitopes and/or fusion partners is used routinely to dissect protein function molecularly. Frequently, the required DNA subcloning is inefficient, especially in cases where multiple constructs are desired for a ... ...

Abstract	Protein tagging with a wide variety of epitopes and/or fusion partners is used routinely to dissect protein function molecularly. Frequently, the required DNA subcloning is inefficient, especially in cases where multiple constructs are desired for a given protein with unique tags. Additionally, the generated clones have unwanted junction sequences introduced. To add versatile tags into the extracellular domain of the transmembrane protein THSD1, we developed a protein tagging technique that utilizes non-classical type IIS restriction enzymes that recognize non-palindromic DNA sequences and cleave outside of their recognition sites. Our results demonstrate that this method is highly efficient and can precisely fuse any tag into any position of a protein in a scarless manner. Moreover, this method is cost-efficient and adaptable because it uses commercially available type IIS restriction enzymes and is compatible with the traditional cloning system used by many labs. Therefore, precision tagging technology will benefit a number of researchers by providing an alternate method to integrate an array of tags into protein expression constructs.
MeSH term(s)	Cells, Cultured ; Cloning, Molecular/methods ; Deoxyribonucleases, Type II Site-Specific/metabolism ; HEK293 Cells ; Humans ; Thrombospondins/biosynthesis ; Thrombospondins/genetics
Chemical Substances	THSD1 protein, human ; Thrombospondins ; Deoxyribonucleases, Type II Site-Specific (EC 3.1.21.4)
Language	English
Publishing date	2017--12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2017.05.153
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 116: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Environmental characterization of home range of Antillean manatees (Trichechus manatus) released in northeastern Brazil.

Santos, Sebastião S Dos / Medeiros, Iara S / Almeida, Isis C DE / Rebelo, Vanessa A / Carvalho, Allan O B / Menezes, Rafael / Marmontel, Miriam / Borges, João Carlos G

Anais da Academia Brasileira de Ciencias

2023 Volume 95, Issue suppl 1, Page(s) e20220574

Abstract: The Antillean manatee occurs discontinuously from the state of Amapá to the state of Alagoas on the coast of Brazil. There is also evidence of reintroduced manatees using the coasts of Sergipe and Bahia, with a preference for calm shallow waters. This ... ...

Abstract	The Antillean manatee occurs discontinuously from the state of Amapá to the state of Alagoas on the coast of Brazil. There is also evidence of reintroduced manatees using the coasts of Sergipe and Bahia, with a preference for calm shallow waters. This study characterized the home range areas of six rehabilitated manatees released in northeastern Brazil. The activities were conducted in the states of Paraíba, Sergipe, and Bahia. Type of environment, substrate, depth, aquatic vegetation, physicochemical variables of the water, presence of solid waste, human settlements, and watercraft were considered to characterize the areas. The results showed a manatee preference for sheltered areas. Resources were available in larger quantities in the dry season, and a reduction in the availability of food items was fund over the years. High overlap was found in the multivariate space of the individuals in terms of the characteristics of the habitats. The estuary of the Paraíba River and the coastal area of Cabedelo Beach in Paraíba showed the greatest amount of solid waste, human settlements, and watercraft. Released manatees exhibited a preference for sites shallower than two meters, with food resources and fresh water availability.
MeSH term(s)	Humans ; Animals ; Trichechus manatus ; Brazil ; Homing Behavior ; Solid Waste ; Trichechus
Chemical Substances	Solid Waste
Language	English
Publishing date	2023-09-15
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2046885-4
ISSN	1678-2690 ; 0001-3765
ISSN (online)	1678-2690
ISSN	0001-3765
DOI	10.1590/0001-3765202320220574
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent Focal Adhesion Assembly.

Rui, Yan-Ning / Xu, Zhen / Fang, Xiaoqian / Menezes, Miriam R / Balzeau, Julien / Niu, Airu / Hagan, John P / Kim, Dong H

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology

2017 Volume 43, Issue 6, Page(s) 2200–2211

Abstract: Background/aims: We recently discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting ... ...

Abstract	Background/aims: We recently discovered that harmful variants in THSD1 (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic patients with supporting evidence from two vertebrate models. The current study seeks to elucidate how THSD1 and patient-identified variants function molecularly in focal adhesions. Methods: Co-immunostaining and co-immunoprecipitation were performed to define THSD1 subcellular localization and interacting partners. Transient expression of patient-identified THSD1 protein variants and siRNA-mediated loss-of-function THSD1 were used to interrogate gene function in focal adhesion and cell attachment to collagen I in comparison to controls. Results: THSD1 is a novel nascent adhesion protein that co-localizes with several known markers such as FAK, talin, and vinculin, but not with mature adhesion marker zyxin. Furthermore, THSD1 forms a multimeric protein complex with FAK/talin/vinculin, wherein THSD1 promotes talin binding to FAK but not to vinculin, a key step in nascent adhesion assembly. Accordingly, THSD1 promotes mature adhesion formation and cell attachment, while its rare variants identified in aneurysm patients show compromised ability. Interestingly, THSD1 also localizes at different stages of endosomes. Clathrin-mediated but not caveolae-mediated endocytosis pathway is involved in THSD1 intracellular trafficking, which positively regulates THSD1-induced focal adhesion assembly, in contrast to the traditional role of endosomes in termination of integrin signals. Conclusions: The data suggest that THSD1 functions at the interface between endosome dynamics and nascent focal adhesion assembly that is impaired by THSD1 rare variants identified from intracranial aneurysm patients.
MeSH term(s)	Clathrin/metabolism ; Endocytosis ; Endosomes/metabolism ; Focal Adhesion Kinase 1/metabolism ; Focal Adhesions/chemistry ; Focal Adhesions/metabolism ; HEK293 Cells ; HeLa Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; Immunoprecipitation ; Intracranial Aneurysm/genetics ; Intracranial Aneurysm/pathology ; Microscopy, Fluorescence ; RNA Interference ; RNA, Small Interfering/metabolism ; Talin/metabolism ; Thrombospondins/antagonists & inhibitors ; Thrombospondins/genetics ; Thrombospondins/metabolism ; Vinculin/metabolism
Chemical Substances	Clathrin ; RNA, Small Interfering ; THSD1 protein, human ; Talin ; Thrombospondins ; Vinculin (125361-02-6) ; Focal Adhesion Kinase 1 (EC 2.7.10.2)
Language	English
Publishing date	2017-10-25
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1067572-3
ISSN	1421-9778 ; 1015-8987
ISSN (online)	1421-9778
ISSN	1015-8987
DOI	10.1159/000484298
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3160: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry

Le Pen, Jérémie / Paniccia, Gabrielle / Bauer, Michael / Hoffmann, H.-Heinrich / Kinast, Volker / Moncada-Velez, Marcela / Pinharanda, Ana / Ricardo-Lax, Inna / Stenzel, Ansgar F. / Rosado-Olivieri, Edwin A. / Ashbrook, Alison W. / Dinnon, Kenneth H. / Doyle, William C. / Freije, Catherine A. / Hong, Seon-Hui / Lee, Danyel / Lewy, Tyler / Luna, Joseph M. / Peace, Avery /

Schmidt, Carltin / Schneider, William M. / Winkler, Roni / Larson, Chloe / McGinn, Timothy / Menezes, Miriam-Rose / Ramos-Espiritu, Lavoisier / Banerjee, Priyam / Poirier, John T. / Sànchez-Rivera, Francisco J. / Zhang, Qian / Casanova, Jean-Laurent / Carroll, Thomas S. / Glickman, J. Fraser / Michailidis, Eleftherios / Razooky, Brandon / MacDonald, Margaret R. / Rice, Charles M.

bioRxiv

Abstract: Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 ... ...

Abstract	Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Finally, we discuss the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.
Keywords	covid19
Language	English
Publishing date	2024-02-20
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.02.16.580725
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: A Genome-Wide Arrayed CRISPR Screen Reveals PLSCR1 as an Intrinsic Barrier to SARS-CoV-2 Entry

Le Pen, Jeremie / Paniccia, Gabrielle / Bauer, Michael / Hoffmann, H.-Heinrich / Kinast, Volker / Moncada-Velez, Marcela / Pinharanda, Ana / Ricardo-Lax, Inna / Stenzel, Ansgar F / Rosado-Olivieri, Edwin A / Ashbrook, Alison W / Dinnon, Kenneth H / Doyle, William / Freije, Catherine / Hong, Seon-Hui / Lee, Danyel / Lewy, Tyler / Luna, Joseph M / Peace, Avery /

Schmidt, Carltin / Schneider, William M / Winkler, Roni / Larson, Chloe / McGinn, Timothy / Menezes, Miriam-Rose / Ramos-Espiritu, Lavoisier / Banerjee, Priyam / Poirier, John T / Sanchez-Rivera, Francisco J / Zhang, Qian / Casanova, Jean-Laurent / Carroll, Thomas S / Glickman, J. Fraser / Michailidis, Eleftherios / Razooky, Brandon / MacDonald, Margaret R / Rice, Charles M

bioRxiv

Abstract	Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence SARS-CoV-2 infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of COVID-19 patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 over-expression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Finally, we discuss the association between PLSCR1 variants and severe COVID-19 cases reported in a recent GWAS.
Keywords	covid19
Language	English
Publishing date	2024-02-20
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.02.16.580725
Database	COVID19

Full text online

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

Kategorien

Inter-library loan at ZB MED

Full text online

Kategorien

Inter-library loan at ZB MED