The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition
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{"title"=>"The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition", "type"=>"journal", "authors"=>[{"first_name"=>"John B.", "last_name"=>"Moldovan", "scopus_author_id"=>"6603325519"}, {"first_name"=>"John V.", "last_name"=>"Moran", "scopus_author_id"=>"7402046149"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"sgr"=>"84930817295", "doi"=>"10.1371/journal.pgen.1005121", "pui"=>"604817685", "pmid"=>"25951186", "scopus"=>"2-s2.0-84930817295", "issn"=>"15537404"}, "id"=>"91a8d89e-256b-330a-be6c-38f901482f3c", "abstract"=>"Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome. To investigate the interplay between the L1 retrotransposition machinery and the host cell, we used co-immunoprecipitation in conjunction with liquid chromatography and tandem mass spectrometry to identify cellular proteins that interact with the L1 first open reading frame-encoded protein, ORF1p. We identified 39 ORF1p-interacting candidate proteins including the zinc-finger antiviral protein (ZAP or ZC3HAV1). Here we show that the interaction between ZAP and ORF1p requires RNA and that ZAP overexpression in HeLa cells inhibits the retrotransposition of engineered human L1 and Alu elements, an engineered mouse L1, and an engineered zebrafish LINE-2 element. Consistently, siRNA-mediated depletion of endogenous ZAP in HeLa cells led to a ~2-fold increase in human L1 retrotransposition. Fluorescence microscopy in cultured human cells demonstrated that ZAP co-localizes with L1 RNA, ORF1p, and stress granule associated proteins in cytoplasmic foci. Finally, molecular genetic and biochemical analyses indicate that ZAP reduces the accumulation of full-length L1 RNA and the L1-encoded proteins, yielding mechanistic insight about how ZAP may inhibit L1 retrotransposition. Together, these data suggest that ZAP inhibits the retrotransposition of LINE and Alu elements.", "link"=>"http://www.mendeley.com/research/zincfinger-antiviral-protein-zap-inhibits-line-alu-retrotransposition", "reader_count"=>50, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>2, "Student > Master"=>5, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>2, "Student > Master"=>5, "Student > Bachelor"=>4, "Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>10, "Agricultural and Biological Sciences"=>33, "Medicine and Dentistry"=>2, "Chemistry"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>33}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"France"=>1, "Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2059430", "https://ndownloader.figshare.com/files/2059431", "https://ndownloader.figshare.com/files/2059432", "https://ndownloader.figshare.com/files/2059433", "https://ndownloader.figshare.com/files/2059434", "https://ndownloader.figshare.com/files/2059435"], "description"=>"<div><p>Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome. To investigate the interplay between the L1 retrotransposition machinery and the host cell, we used co-immunoprecipitation in conjunction with liquid chromatography and tandem mass spectrometry to identify cellular proteins that interact with the L1 first open reading frame-encoded protein, ORF1p. We identified 39 ORF1p-interacting candidate proteins including the zinc-finger antiviral protein (ZAP or ZC3HAV1). Here we show that the interaction between ZAP and ORF1p requires RNA and that ZAP overexpression in HeLa cells inhibits the retrotransposition of engineered human L1 and Alu elements, an engineered mouse L1, and an engineered zebrafish LINE-2 element. Consistently, siRNA-mediated depletion of endogenous ZAP in HeLa cells led to a ~2-fold increase in human L1 retrotransposition. Fluorescence microscopy in cultured human cells demonstrated that ZAP co-localizes with L1 RNA, ORF1p, and stress granule associated proteins in cytoplasmic foci. Finally, molecular genetic and biochemical analyses indicate that ZAP reduces the accumulation of full-length L1 RNA and the L1-encoded proteins, yielding mechanistic insight about how ZAP may inhibit L1 retrotransposition. Together, these data suggest that ZAP inhibits the retrotransposition of LINE and Alu elements.</p></div>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408141, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005121.s001", "https://dx.doi.org/10.1371/journal.pgen.1005121.s002", "https://dx.doi.org/10.1371/journal.pgen.1005121.s003", "https://dx.doi.org/10.1371/journal.pgen.1005121.s004", "https://dx.doi.org/10.1371/journal.pgen.1005121.s005", "https://dx.doi.org/10.1371/journal.pgen.1005121.s006"], "stats"=>{"downloads"=>33, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Zinc_Finger_Antiviral_Protein_ZAP_Inhibits_LINE_and_Alu_Retrotransposition_/1408141", "title"=>"The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059388"], "description"=>"<p><i>(A) Schematic of the cultured-cell retrotransposition assay</i>: HeLa cells were transfected with an engineered human L1.3 construct (pJJ101/L1.3) marked with a blasticidin indicator cassette (<i>mblastI</i>). The pJJ101/L1.3 construct was cloned into a pCEP4 mammalian expression vector. A CMV promoter augments L1 expression and an SV40 polyadenylation signal (pA) is located downstream of the native L1 polyadenylation signal. The <i>mblastI</i> cassette is cloned into the L1 3' UTR antisense to the L1 and contains a blasticidin deaminase gene that is disrupted by an intron in the L1 sense orientation. The blasticidin deaminase gene can only be expressed when the L1 transcript is spliced, reverse transcribed, and inserted into genomic DNA [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005121#pgen.1005121.ref030\" target=\"_blank\">30</a>,<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005121#pgen.1005121.ref071\" target=\"_blank\">71</a>]. <i>(B) Schematic of the pJJ101/L1</i>.<i>3 retrotransposition screen</i>: To analyze the effect of the ORF1p-FLAG interacting proteins on L1 retrotransposition, HeLa cells were co-transfected with equal amounts of pJJ101/L1.3 and a cDNA plasmid expressing one of the candidate ORF1p-FLAG interacting proteins or a pCEP4 empty vector. To control for potential off-target effects, HeLa cells also were co-transfected with a control plasmid (pcDNA6/TR) that expresses the blasticidin deaminase gene and a cDNA plasmid expressing one of the candidate proteins or a pCEP4 empty vector. Both assays were subjected to the same blasticidin selection regimen. The resultant number of blasticidin-resistant colonies in pcDNA6/TR control assays provides a visual, quantitative readout of the effect of cDNA overexpression on the ability of cells to grow in the presence of blasticidin. <i>(C) Results of pJJ101/L1</i>.<i>3 retrotransposition screen</i>: HeLa cells were co-transfected with pJJ101/L1.3 and each of the indicated cDNA expressing plasmids. L1 retrotransposition was assayed in 6-well tissue culture plates. The X-axis indicates the cDNA that was co-transfected with pJJ101/L1.3. The bracketed number next to each cDNA indicates the number of independent experiments. The Y-axis indicates L1 retrotransposition activity after accounting for cDNA toxicity (see Fig 2B). Retrotransposition activity (black bars) is normalized to the pCEP4 empty vector control. Error bars represent the standard deviation for each set of experiments. The red dotted line indicates a 50% inhibition of retrotransposition activity.</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408104, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g002", "stats"=>{"downloads"=>1, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Several_of_the_ORF1p_FLAG_interacting_proteins_inhibit_L1_retrotransposition_/1408104", "title"=>"Several of the ORF1p-FLAG interacting proteins inhibit L1 retrotransposition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059376"], "description"=>"<p><i>(A) Schematic of L1 constructs</i>: pJM101/L1.3 expresses a human L1 (L1.3) [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005121#pgen.1005121.ref005\" target=\"_blank\">5</a>] containing an <i>mneoI</i> retrotransposition indicator cassette within the L1 3' UTR. The pJM101/L1.3FLAG construct is identical to pJM101/L1.3, but contains a single FLAG epitope on the carboxyl-terminus of ORF1p. Both constructs were cloned into a pCEP4 mammalian expression vector. A CMV promoter augments L1 expression and an SV40 polyadenylation signal (pA) is located downstream of the native L1 polyadenylation signal. <i>(B) Results of immunoprecipitation experiments</i>: Whole cell lysates from HeLa cells transfected with either pJM101/L1.3 or pJM101/L1.3FLAG were subjected to immunoprecipitation using an anti-FLAG antibody. The proteins then were separated by SDS-PAGE, visualized by silver staining, and subjected to LC-MS/MS. An ~40 kDa band corresponding to the theoretical molecular weight of ORF1p is visible in the pJM101/L1.3FLAG lane (*). Black bars indicate the approximate molecular weights of the ORF1p-FLAG interacting proteins. Molecular weight standards (kDa) are shown on the left hand side of the gel. <i>(C) Validation of the ORF1p-FLAG immunoprecipitation</i>: Western blot experiments using an antibody specific to amino acids 31–49 of L1.3 ORF1p verified the enrichment of ORF1p-FLAG in pJM101/L1.3FLAG, but not pJM101/L1.3 immunoprecipitation reactions. Cells transfected with the pCEP4 vector served as a negative control. <i>(D) Validation of putative ORF1p-FLAG interacting proteins</i>: Western blot images of the pJM101/L1.3FLAG and pJM101/L1.3 immunoprecipitation (IP) reactions. The pCEP4 lanes denote whole cell lysates derived from HeLa cells transfected with an empty pCEP4 vector (~ 1.0% input). Primary antibodies used to probe western blots are indicated to the left of the images. Immunoprecipitation reactions were conducted in either the absence (left) or presence (right) of RNaseA (10 μg/mL). The putative cellular functions of the ORF1p-FLAG interacting proteins are indicated on the right hand side of the blots.</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408102, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g001", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_identification_of_host_proteins_immunoprecipitated_with_L1_ORF1p_FLAG_/1408102", "title"=>"The identification of host proteins immunoprecipitated with L1 ORF1p-FLAG.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059395"], "description"=>"<p><i>(A) Schematic of pJM101/L1</i>.<i>3Δneo</i>: Bold black lines indicate the approximate location of probes (5UTR99 and ORF2_5804) used in the northern blot experiments. pJM101/L1.3Δneo is expressed from a pCEP4 vector. A CMV promoter augments L1 expression and an SV40 polyadenylation signal (pA) is located downstream of the native L1 polyadenylation signal. <i>(B) Results of northern blots</i>: Top panel: HeLa cells were co-transfected with pJM101/L1.3Δneo and either the indicated ZAP-S expression plasmids or an empty pCEP4 vector. Northern blot images depict the effect of ZAP-S overexpression on polyadenylated L1 RNA levels. The constructs transfected into HeLa cells are indicated above each lane. UTF indicates untransfected HeLa cells and serves as a negative control. Probes (5UTR99 and ORF2_5804) are indicated in the top left corner of the respective blots. The black arrow indicates the position of the full-length L1 RNA. The blue and yellow arrows indicate shorter L1 RNA species. The experiment was repeated three times with similar results. Actin served as a loading control. RNA size standards (~kb) are shown at the right of the blot image. Bottom panel: Quantification of northern blot bands. The X-axis indicates the cDNA expression construct that was co-transfected with pJM101/L1.3Δneo. The Y-axis indicates relative band intensity normalized to pCEP4 controls (100%). Black bars represent the full-length L1 band. Blue and yellow bars represent the smaller L1 RNA bands, corresponding to the colored arrows, respectively, in the top panel. The results are the average of three independent experiments. Error bars represent standard deviations. <i>(C) Schematic of pJBM2TE1</i>: The construct contains a T7 epitope tag on the carboxyl-terminus of ORF1p and a TAP tag on the carboxyl-terminus of ORF2p. An <i>mneoI</i> retrotransposition indicator cassette is present in the 3’ UTR. pJMB2TE1 is expressed from a pCEP4 backbone, which has been modified to contain a puromycin selectable marker. A CMV promoter augments L1 expression and an SV40 polyadenylation signal (pA) is located downstream of the native L1 polyadenylation signal. <i>(D) ZAP-S decreases the accumulation of the L1-encoded proteins</i>: HeLa cells were co-transfected with pJBM2TE1 and the plasmids indicated above each lane. UTF indicates untransfected HeLa cells and serves as a negative control. Depicted are western blots using whole cell lysates (WCL, top panel) or RNP fractions (RNP, bottom panel). Blue arrows indicate the positions of ORF2p, ORF1p, ZAP-S, and ZAP-S/∆72–372. The eIF3 protein is used as a loading control. Representative images are shown. The experiments were repeated three times with similar results.</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408111, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g004", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_ZAP_S_on_L1_RNA_and_L1_protein_expression_/1408111", "title"=>"The effect of ZAP-S on L1 RNA and L1 protein expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059391"], "description"=>"<p><i>(A) ZAP inhibits L1 retrotransposition</i>: Top panel: Schematics of ZAP constructs. Depicted are the relative positions of the zinc-finger domains (light gray rectangles), cysteine-histidine (CCCH) zinc-fingers (vertical black bars), and PARP-like domain (dark gray rectangles) of the ZAP-L and ZAP-S expression constructs. ZAP-L contains a carboxyl-terminal HA tag (blue rectangle labeled HA). The ZAP-S/1-311 construct contains an additional 31 amino acids at the carboxyl terminus. The ZAP-S/∆72–372 harbors a deletion that removes the CCCH zinc fingers (See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005121#sec013\" target=\"_blank\">Methods</a>). Middle panel: Results of the retrotransposition assays. The X-axis indicates the cDNA co-transfected with pJJ101/L1.3 or pcDNA6/TR. The Y-axis indicates pJJ101/L1.3 retrotransposition activity (black bars), or pcDNA6/TR colony formation activity (white bars). All values have been normalized to the pCEP4 empty vector control (100%). The numbers above the bar graphs indicate the number of independent experiments performed with each cDNA expression construct. Error bars represent standard deviations. Bottom panel: A single well of a representative six-well tissue culture plate, displaying blasticidin-resistant colonies from the pJJ101/L1.3 retrotransposition assay (top, black rectangle) and the pcDNA6/TR control assay (bottom, white rectangle). <i>(B) ZAP inhibits Alu retrotransposition</i>: The X-axis indicates the cDNA co-transfected with pJM101/L1.3Δneo and pAlu<i>neo</i><sup>Tet</sup>. The Y-axis indicates the retrotransposition efficiency. All values are normalized to the pCEP4 empty vector control (100%). Control assays using a plasmid that expresses the neomycin phosphotransferase gene (pcDNA3) were conducted similarly to pcDNA6/TR control assays as outlined in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005121#pgen.1005121.g002\" target=\"_blank\">Fig 2B</a>. Representative images of G418-resistant HeLa foci from the Alu retrotransposition assay are shown below the bar graph. The results are the average of three independent experiments. Error bars indicate standard deviations. <i>(C) ZAP inhibits the retrotransposition of mouse and zebrafish LINE elements</i>. The X-axis indicates the cDNA that was co-transfected with human L1 (pJM101/L1.3 (black bars)), mouse L1 (pG<sub>F</sub>21 (dark grey bars)), zebrafish L2 (pZfL2-2 (light grey bars)), or synthetic mouse L1 (pCEPsmL1 (white bars)). The Y-axis indicates the retrotransposition efficiency. Representative images of G418-resistant HeLa cell foci are shown below the bar graph. Control assays using a plasmid that expresses the neomycin phosphotransferase gene (pcDNA3) were conducted similarly to pcDNA6/TR control assays outlined in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005121#pgen.1005121.g002\" target=\"_blank\">Fig 2B</a>. All values are normalized to the pCEP4 empty vector control (100%). Error bars indicate standard deviations. <i>(D) The depletion of ZAP enhances L1 retrotransposition</i>: Top panels: Western blots of whole cell lysates derived from mock HeLa cell transfections or HeLa cells transfected with indicated siRNAs. Blue arrows point to the approximate location of ZAP-L and ZAP-S. Bottom panel: The bar graph depicts pLRE-<i>mEGFP1</i> retrotransposition activity following siRNA treatment. The X-axis indicates the siRNA. The Y-axis indicates the pLRE-<i>mEGFP1</i> retrotransposition efficiency normalized to the control siRNA (set to 1). Retrotransposition efficiency values are reported as the mean from four independent experiments. Error bars indicate the standard deviations. Asterisks indicate statistically significant differences from the control siRNA experiments (two-tailed t test/p<0.05).</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408107, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g003", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ZAP_S_inhibits_LINE_and_Alu_retrotransposition_/1408107", "title"=>"ZAP-S inhibits LINE and Alu retrotransposition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059405"], "description"=>"<p>Once a genomic L1 (black rectangle located on the green chromosome) is transcribed, the resultant bicistronic L1 mRNA is exported to the cytoplasm for translation. L1 ORF1p (blue circles) and ORF2p (yellow circle) bind back to L1 mRNA to form an L1 RNP. The L1 RNP gains access to the nucleus where a new L1 copy is inserted into genomic DNA by the process of TPRT (black rectangle located on the blue chromosome). In ZAP-mediated restriction, ZAP (red hexagon) interacts with L1 mRNA in the cytoplasm (1), which we propose leads to the destabilization of L1 RNA (2) and/or a block in translation (?) through the recruitment of other cellular factors (<i>e</i>.<i>g</i>., SG associated proteins, RNA decay proteins) involved in RNA metabolism.</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408121, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g007", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_working_model_for_how_ZAP_restricts_L1_retrotransposition_/1408121", "title"=>"A working model for how ZAP restricts L1 retrotransposition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059403"], "description"=>"<p><i>(A) Co-localization of transfected L1 RNA and ORF1p</i>: ORF1p (red) expressed from pJM101/L1.3 co-localizes with L1 RNA (magenta). <i>(B) Co-localization of transfected L1 RNA and ORF1p with transfected ZAP-S-tGFP in cytoplasmic foci</i>: ORF1p (red) and L1 RNA (magenta) expressed from pJM101/L1.3 co-localize with ZAP-S-tGFP (green). <i>(C-D) The ZAP-S zinc-finger domain is necessary for co-localization with ORF1p</i>: ORF1p (red) and L1 RNA (magenta) expressed from pJM101/L1.3 co-localize with ZAP-S/Δ310-645-tGFP (green) (panel C). ZAP-S/Δ72-372-tGFP (green) diffusely distributes throughout the cytoplasm, while ORF1p (red) expressed from pJM101/L1.3 forms cytoplasmic foci with L1 RNA (magenta) (panel D). The right-most image of each panel represents a merged image. The name of the protein or RNA is indicated at the bottom left, and the name of the primary antibody used (<i>italicized</i>) is annotated at the bottom right of each image. Nuclei were stained with DAPI (blue) and the scale bar represents 25 μM. Experiments were repeated three times with similar results.</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408119, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g006", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_co_localization_of_ZAP_with_L1_RNA_and_ORF1p_in_HeLa_cells_/1408119", "title"=>"The co-localization of ZAP with L1 RNA and ORF1p in HeLa cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/2059399"], "description"=>"<p><i>(A) Co-localization of transfected ORF1p and ZAP-S in HeLa cells</i>: ORF1p (red) expressed from pJM101/L1.3Δneo co-localizes with ZAP-S-tGFP (green). The experiment was repeated five times with similar results. <i>(B) Co-localization of transfected ORF1p with endogenous ZAP in cytoplasmic foci in HeLa cells</i>: ORF1p-T7 (green) expressed from pAD2TE1 co-localizes with endogenous ZAP (red). The experiment was repeated five times with similar results. <i>(C) Co-localization of transfected ZAP-S-tGFP with endogenous ORF1p in cytoplasmic foci in PA-1 cells</i>: ZAP-S-tGFP (green) co-localizes with endogenous ORF1p (red). PA-1 experiments were repeated twice with similar results. <i>(D-E) The ZAP-S zinc-finger domain is necessary for co-localization with ORF1p in HeLa cells</i>: ORF1p (red) expressed from pJM101/L1.3Δneo co-localizes with ZAP-S/Δ310-645-tGFP (green) (panel D). ORF1p (red) expressed from pJM101/L1.3Δneo forms cytoplasmic foci that do not contain ZAP-S/Δ72-372-tGFP (green) (panel E). The right-most image of each panel represents a merged image. The cell type is indicated at the top left (yellow), the protein name is listed on the bottom left, and the name of the primary antibody used (<i>italicized</i>) is annotated at the bottom right. Nuclei were stained with DAPI (blue) and the scale bar represents 25 μM.</p>", "links"=>[], "tags"=>["39 ORF 1p candidate proteins", "Tandem mass spectrometry", "L 1 retrotransposition machinery", "ORF 1p", "zap", "L 1", "zc", "Alu elements", "L 1 RNA", "HeLa cells", "3HAV", "Alu Retrotransposition Long INterspersed Element", "L 1 retrotransposition"], "article_id"=>1408115, "categories"=>["Biological Sciences"], "users"=>["John B. Moldovan", "John V. Moran"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005121.g005", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_co_localization_of_ORF1p_and_ZAP_in_cytoplasmic_foci_/1408115", "title"=>"The co-localization of ORF1p and ZAP in cytoplasmic foci.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-07 03:29:33"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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