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{"title"=>"Circular RNAs co-precipitate with extracellular vesicles: A possible mechanism for circrna clearance", "type"=>"journal", "authors"=>[{"first_name"=>"Erika", "last_name"=>"Lasda", "scopus_author_id"=>"6506137502"}, {"first_name"=>"Roy", "last_name"=>"Parker", "scopus_author_id"=>"7402752503"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"608547678", "isbn"=>"1932-6203", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0148407", "scopus"=>"2-s2.0-84959423367", "pmid"=>"26848835", "sgr"=>"84959423367"}, "id"=>"773b6e2b-8897-3827-bbe5-560e030eed2d", "abstract"=>"Backspliced circular RNAs (circRNAs) are prevalent in many eukaryotic systems and are spliced from thousands of different genes. Where examined, circRNAs are often highly stable and the mechanisms by which cells degrade and/or clear circRNAs from the cells are unknown. Here we investigated the possibility that cells can eliminate circRNAs into extracellular space, possibly within released vesicles such as exosomes and microvesicles. From three different cell lines and examining multiple circRNAs, we show that extracellular vesicle (EVs) preparations recovered from cell culture conditioned media contain established circRNAs. Moreover, these circRNAs are enriched over their linear counterparts within EV preparations when compared to the producing cells. This supports the idea that expulsion from cells into extracellular space, as by EVs release, can be a mechanism by which cells clear circRNAs. Moreover, since EVs can be taken up by other cells, excreted circRNAs could contribute to cell to cell communication.", "link"=>"http://www.mendeley.com/research/circular-rnas-coprecipitate-extracellular-vesicles-possible-mechanism-circrna-clearance", "reader_count"=>95, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Researcher"=>25, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>24, "Student > Postgraduate"=>5, "Student > Master"=>10, "Other"=>4, "Student > Bachelor"=>13, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Researcher"=>25, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>24, "Student > Postgraduate"=>5, "Student > Master"=>10, "Other"=>4, "Student > Bachelor"=>13, "Professor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>3, "Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>39, "Agricultural and Biological Sciences"=>31, "Medicine and Dentistry"=>11, "Neuroscience"=>3, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>3}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Neuroscience"=>{"Neuroscience"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>31}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>39}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Denmark"=>1, "Germany"=>1}, "group_count"=>4}

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• {"files"=>["https://ndownloader.figshare.com/files/4243933"], "description"=>"<p>Target genes and primers used in the study.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596225, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Target_genes_and_primers_used_in_the_study_/2596225", "title"=>"Target genes and primers used in the study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243909"], "description"=>"<div><p>Backspliced circular RNAs (circRNAs) are prevalent in many eukaryotic systems and are spliced from thousands of different genes. Where examined, circRNAs are often highly stable and the mechanisms by which cells degrade and/or clear circRNAs from the cells are unknown. Here we investigated the possibility that cells can eliminate circRNAs into extracellular space, possibly within released vesicles such as exosomes and microvesicles. From three different cell lines and examining multiple circRNAs, we show that extracellular vesicle (EVs) preparations recovered from cell culture conditioned media contain established circRNAs. Moreover, these circRNAs are enriched over their linear counterparts within EV preparations when compared to the producing cells. This supports the idea that expulsion from cells into extracellular space, as by EVs release, can be a mechanism by which cells clear circRNAs. Moreover, since EVs can be taken up by other cells, excreted circRNAs could contribute to cell to cell communication.</p></div>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596201, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407", "stats"=>{"downloads"=>3, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Circular_RNAs_Co_Precipitate_with_Extracellular_Vesicles_A_Possible_Mechanism_for_circRNA_Clearance/2596201", "title"=>"Circular RNAs Co-Precipitate with Extracellular Vesicles: A Possible Mechanism for circRNA Clearance", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243912"], "description"=>"<p>Preparations enriched in EVs were precipitated from conditioned media from HeLa, 293T, or U-2 OS cultured cells. Isolated RNA was used for RT-PCR with divergent primers to detect indicated backspliced circRNAs. Products were visualized by ethidium bromide on an agarose gel. A selection of previously identified circRNAs were chosen for analysis. Gene names and circRNA IDs shown are according to the circBase database (<a href=\"http://circbase.org/\" target=\"_blank\">http://circbase.org/</a>) [<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0148407#pone.0148407.ref015\" target=\"_blank\">15</a>]. -RT lanes omitted reverse transcriptase.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596204, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/circRNAs_are_detected_in_preparations_enriched_in_extracellular_vesicles_/2596204", "title"=>"circRNAs are detected in preparations enriched in extracellular vesicles.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243915"], "description"=>"<p>(A) Electron microscopy of vesicles with a typical cup-shaped morphology in a variety of sizes consistent with exosomes and microvesicles. Representative examples of smaller and larger vesicles are shown. Scale bars are 100 nm. (B) Nanoparticle Tracking Analysis profiles of particle size and distribution in each sample are characteristic of small extracellular vesicle preparations containing exosomes and microvesicles. Different colored traces represent three different video captures of the same sample. (C) Venn diagram of the list of GO term “extracellular exosome” (GO:0070062) cellular component proteins (2736 proteins, blue circles) compared to the list of the top 100 most abundant proteins (green circles) identified by mass spectrometry analysis of each EV precipitated sample. The number of overlapping proteins is indicated within each intersecting region.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596207, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Precipitated_preparations_from_conditioned_cell_culture_media_from_HeLa_293T_or_U_2_OS_cells_show_characteristic_particle_morphology_size_and_protein_composition_of_extracellular_vesicles_including_exosomes_30_100_nm_and_microvesicles_100_1000_nm_/2596207", "title"=>"Precipitated preparations from conditioned cell culture media from HeLa, 293T, or U-2 OS cells show characteristic particle morphology, size, and protein composition of extracellular vesicles, including exosomes (30–100 nm) and microvesicles (100–1000 nm).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243918"], "description"=>"<p>RNA isolated from EV preparations and corresponding source cells was analyzed by real-time quanitative RT-PCR for indicated backspliced circRNAs and the linear spliced mRNA counterparts of the same gene. (A) The relative quantity of each RNA is shown with the level in cells plotted on the primary (left) axis and in EVs on the secondary (right) axis of each bar graph. Error bars are standard deviation of triplicate reactions. (B) Fold enrichment of circRNAs compared to the linear spliced counterpart RNAs in EVs over their corresponding source cells. Fold enrichment is calculated from the qPCR CT (threshold cycle) values for each sample according to the formula shown.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596210, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/circRNAs_are_enriched_in_EV_preparations_over_linear_counterparts_/2596210", "title"=>"circRNAs are enriched in EV preparations over linear counterparts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243924"], "description"=>"<p>circRNAs formed by nuclear backsplicing events are eliminated from cells by incorporation into vesicles that are released, such as exosomes or microvesicles.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596216, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Possible_mechanisms_for_circRNA_clearance_/2596216", "title"=>"Possible mechanisms for circRNA clearance.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243927"], "description"=>"<p>Mass spectrometry GO terms Cellular Components.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596219, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mass_spectrometry_GO_terms_Cellular_Components_/2596219", "title"=>"Mass spectrometry GO terms Cellular Components.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2016-02-05 19:41:02"}
• {"files"=>["https://ndownloader.figshare.com/files/4243930"], "description"=>"<p>circRNAs used in this study.</p>", "links"=>[], "tags"=>["circRNA Clearance Backspliced", "extracellular space", "EV"], "article_id"=>2596222, "categories"=>["Biophysics", "Physical Sciences not elsewhere classified", "Cell Biology", "Genetics", "Molecular Biology", "Physiology", "Biological Sciences not elsewhere classified", "Developmental Biology", "Cancer", "Hematology"], "users"=>["Erika Lasda", "Roy Parker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0148407.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/circRNAs_used_in_this_study_/2596222", "title"=>"circRNAs used in this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2016-02-05 19:41:02"}

PMC Usage Stats | Further Information

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• {"unique-ip"=>"23", "full-text"=>"20", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}
• {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"9"}
• {"unique-ip"=>"18", "full-text"=>"15", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"10"}
• {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2020", "month"=>"11"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}

F1000Prime