CERKL, a Retinal Disease Gene, Encodes an mRNA-Binding Protein That Localizes in Compact and Untranslated mRNPs Associated with Microtubules
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{"title"=>"CERKL, a retinal disease gene, encodes an mRNA-binding protein that localizes in compact and untranslated mRNPs associated with microtubules", "type"=>"journal", "authors"=>[{"first_name"=>"Alihamze", "last_name"=>"Fathinajafabadi", "scopus_author_id"=>"56082265100"}, {"first_name"=>"Eva", "last_name"=>"Pérez-Jiménez", "scopus_author_id"=>"7801403917"}, {"first_name"=>"Marina", "last_name"=>"Riera", "scopus_author_id"=>"35427754200"}, {"first_name"=>"Erwin", "last_name"=>"Knecht", "scopus_author_id"=>"7007028649"}, {"first_name"=>"Roser", "last_name"=>"Gonzàlez-Duarte", "scopus_author_id"=>"7006670820"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"372485563", "pmid"=>"24498393", "doi"=>"10.1371/journal.pone.0087898", "sgr"=>"84896818865", "scopus"=>"2-s2.0-84896818865"}, "id"=>"dc1ac343-f6e5-3512-9f44-e22defe87deb", "abstract"=>"The function of CERKL (CERamide Kinase Like), a causative gene of retinitis pigmentosa and cone-rod dystrophy, still awaits characterization. To approach its cellular role we have investigated the subcellular localization and interaction partners of the full length CERKL isoform, CERKLa of 532 amino acids, in different cell lines, including a photoreceptor-derived cell line. We demonstrate that CERKLa is a main component of compact and untranslated mRNPs and that associates with other RNP complexes such as stress granules, P-bodies and polysomes. CERKLa is a protein that binds through its N-terminus to mRNAs and interacts with other mRNA-binding proteins like eIF3B, PABP, HSP70 and RPS3. Except for eIF3B, these interactions depend on the integrity of mRNAs but not of ribosomes. Interestingly, the C125W CERKLa pathological mutant does not interact with eIF3B and is absent from these complexes. Compact mRNPs containing CERKLa also associate with microtubules and are found in neurites of neural differentiated cells. These localizations had not been reported previously for any member of the retinal disorders gene family and should be considered when investigating the pathogenic mechanisms and therapeutical approaches in these diseases.", "link"=>"http://www.mendeley.com/research/cerkl-retinal-disease-gene-encodes-mrnabinding-protein-localizes-compact-untranslated-mrnps-associat", "reader_count"=>26, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>3, "Student > Bachelor"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>3, "Psychology"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4357618"], "description"=>"<p><b>A</b> and <b>B</b>) Colocalization of CERKL (HA) with three markers of SGs (PABP and eIF4E, detected with specific antibodies described in the Materials and Methods section), and the mRNAs poly(A) tail, detected with oligo(dT) FISH (upper, middle and lower panels, respectively) in COS-7 cells overexpressing CERKL-HA, either untreated (<b>A</b>) or incubated with 500 µM sodium arsenite for 30 min (<b>B</b>). <b>C</b>) The localizations of PABP and CERKL (HA) in transfected 661W mouse photoreceptor derived cells were compared by immunofluorescence. Images at higher magnification of the rectangles in the upper row are shown below. <b>D</b>) COS-7 cells transfected with CERKL-HA were untreated (MOCK) or treated for 30 min with 100 µg/mL cycloheximide (CHX) and the localizations by immunofluorescence of PABP and CERKL (HA) were compared. <b>E</b>) COS-7 cells were transfected with CERKL-HA and treated with sodium arsenite as in <b>B</b>. The localizations by immunofluorescence of CERKL (HA) and the P-body marker EDC4 were compared. Images at higher magnification of the rectangles in the upper row are shown below. Arrowheads indicate various colocalizations. All bars: 10 µm.</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>924389, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g001"], "stats"=>{"downloads"=>2, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CERKL_localizes_to_SGs_and_P_bodies_/924389", "title"=>"CERKL localizes to SGs and P-bodies.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357621"], "description"=>"<p><b>A</b>) COS-7 cells overexpressing CERKL-HA were mock-treated (upper row) or treated for 2 h with 40 nM leptomycin B (LeptB), 1 µg/mL actinomycin D (ActD) or 100 µg/mL alpha-amanitin (α-Aman). Then, the localizations of CERKL (HA) and PABP (marker of SGs) were investigated by immunofluorescence. <b>B</b>) COS-7 cells overexpressing the CERKL-C125W mutant were mock-treated or treated with 500 µM SA for 30 min and the localizations of the mutant CERKL (CERKL C125W-HA) and PABP (upper panels) or eIF4E (lower panels) were investigated by immunofluorescence. Images at higher magnification of the rectangles are shown on the right. All bars: 10 µm.</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926182, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g002"], "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Formation_of_SGs_by_overexpression_of_CERKL_requires_the_nuclear_import_export_of_the_protein_/926182", "title"=>"Formation of SGs by overexpression of CERKL requires the nuclear import/export of the protein.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357624"], "description"=>"<p><b>A</b>) HeLa cells stably expressing CERKL WT-HA or an N-terminal fragment of the protein (CERKL 1-256-HA), generated as described in the Materials and Methods section, were lysed and polysomes were isolated by centrifugation in a 0.5-1.3-1.7-2.1 M discontinuous sucrose gradient. Seven 1 ml fractions (1–7) and the pellet (P) were analyzed by immunoblot using antibodies that recognize HA, the ribosomal protein RPS6. Actin was used as control. <b>B</b> and <b>C</b>) Similar experiments were carried out incubating the cell lysates with EDTA (15 mM) (<b>B</b>) or RNase A (100 µg/mL) (<b>C</b>) before centrifugation. Antibodies that recognize HA and the ribosomal proteins RPS6 and RPL26 were used. <b>D</b>–<b>F</b>) The pellet (<b>D</b>) and fractions 2 and 3 of the gradient (<b>E</b> and <b>F</b>) were treated with 25 mM (<b>D</b> and <b>E</b>) or 450 mM (<b>F</b>) NaCl, with or without RNase A (100 µg/mL) and subsequently centrifuged in a continuous sucrose density gradient (0.3–1.5 M) as described in Materials and Methods. The new fractions (1–11, in <b>D</b> and 1–10, in <b>E</b> and <b>F</b>) and the pellet (P) were immunoblotted with HA and RPS6 (<b>D</b>) or RNase A (<b>E</b> and <b>F</b>) antibodies. Below the Western blots, the concentration of RNA quantified at 260 nm is shown. <b>G</b>) The same experiment as in <b>E</b> and <b>F</b>, with fractions 2 and 3 treated with 30 mM EDTA or 1 mM puromycin at 25 mM and 450 mM NaCl before the continuous sucrose gradient. Ten fractions and the pellet were analyzed by immunoblot using antibodies that recognize HA.</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926183, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g003"], "stats"=>{"downloads"=>6, "page_views"=>286, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CERKL_localizes_to_polysomes_and_compact_mRNPs_/926183", "title"=>"CERKL localizes to polysomes and compact mRNPs.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357630"], "description"=>"<p><b>A</b>) HEK-293T cells overexpressing Flag-tagged GFP, CERKL- WT or CERKL-C125W were lysed and Flag was immunoprecipitated as described in Materials and Methods, analyzed by SDS-PAGE in 8% (left panel) and 20% (right panel) polyacrylamide gels and silver-stained. Proteins were characterized by mass spectrometry (see Materials and Methods). The positions of the proteins are indicated by arrows, from up to down as follows: eIF3B (1), CERKL (2), alpha-tubulin (3), ß-tubulin (4) (8%polyacrylamide gel), PABP (5), HSP70 (6), CERKL (7) and RPS3 (8) (20% polyacrylamide gel, WT lane) and GFP (9) (20% polyacrylamide gel, GFP lane). <b>B</b>) Flag immunoprecipitations (FLAG IP) of protein homogenates from HEK 293T cells transfected with CERKL-Flag (WT), CERKL-C125W-Flag (CW) or, as a control, GFP-Flag (GFP). The position of CERKL and GFP, detected with anti-Flag, is shown. Specific antibodies were used to detect eIF3B, PABP, HSP70 and RPS3. <b>C</b>) EMSA of CERKL protein incubated at the indicated concentrations with biotinylated mRNAs from human retina. BSA (CONTROL) and His-MBP (0) were used as negative controls. Addition of an excess of non-biotinylated probes reduced the intensity of the shifted bands (COMPETITION). Arrowheads indicate the position of the shifted bands. <b>D</b>) Two CERKL proteins moieties, Nter (amino acids 1–256) and Cter (amino acids 252–532) and the two negative controls from <b>C</b> were analyzed by EMSA using biotinylated mRNAs from COS-7 cells. Arrowhead indicates the position of the shifted band. <b>E</b>) Flag-tagged CERKL-WT or GFP proteins transiently expressed in HEK 293T cells were purified by immunoprecipitation, eluted with Flag peptide and then incubated with m<sup>7</sup>-GTP bound to Sepharose 4B beads (M7-GTP). Proteins bound to these beads were analyzed by Western blot with anti-Flag. As control, unconjugated Sepharose 4B beads (Seph) were used. Only CERKL-WT-Flag, but not GFP-Flag, binds to m<sup>7</sup>-GTP-Sepharose.</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926184, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g004"], "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CERKL_interacts_with_components_of_the_translation_machinery_and_with_mRNAs_/926184", "title"=>"CERKL interacts with components of the translation machinery and with mRNAs.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357633"], "description"=>"<p><b>A</b> and <b>B</b>) HEK-293T cells were transfected with CERKL-WT (<b>A</b>) or with CERKL-C125W mutant (<b>B</b>). After 48 h, cells were treated with 100 µg/ml cycloheximide and lysates were treated or not with RNase A (100 µg/mL) in the presence of three different concentrations of NaCl (150, 450 and 600 mM, as indicated). Then, the lysates were immunoprecipitated with anti-Flag M2 affinity beads. The co-immunoprecipitated proteins were analyzed by immunoblot using antibodies that recognize eIF3B (only in <b>A</b>), PABP, HSP70, RPS3 and Flag (to detect CERKL-WT and its C125W mutant). In the histograms below, the bands corresponding to the various proteins recovered after the Flag IP, in the presence of RNase A, were quantified with respect to CERKL-WT (<b>A</b>) or CERKL-C125W (<b>B</b>) in each lane. Values are the mean from 4 different experiments. Stars indicate statistically significant differences from the values in the presence of 150 mM NaCl (*p<0.05, **p<0.01 and ***p<0.005).</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926186, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g005"], "stats"=>{"downloads"=>3, "page_views"=>34, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_the_compact_mRNPs_CERKL_interacts_with_PABP_HSP70_and_RPS3_in_an_mRNA_dependent_manner_/926186", "title"=>"In the compact mRNPs, CERKL interacts with PABP, HSP70 and RPS3 in an mRNA-dependent manner.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357636"], "description"=>"<p><b>A</b>) COS-7 cells overexpressing CERKL were fixed with 2% paraformaldehyde and the localizations of CERKL (HA) and ß-tubulin were compared by immunofluorescence. As control, cells were treated with 1 µg/ml colchicine (COL) for 2 h to disrupt microtubules. Bar: 10 µm. <b>B</b>) CERKL colocalizes with microtubule-related structures. COS-7 transfected cells were fixed with 2% paraformaldehyde and the localization of CERKL (HA) was compared by immunofluorescence with that of acetyl-α-tubulin (upper panels) and the centrosomal protein pericentrin (lower panels, arrowhead) using specific antibodies. Images at higher magnification of the rectangles in the upper row are shown below. All bars: 10 µm. <b>C</b>) Immunoblot of alpha and ß-tubulin, eIF3B, PABP, HSP70 and RPS3 proteins co-immunoprecipitating with CERKL-Flag or GFP-Flag in the presence (+) or not (−) of 1 µg/ml colchicine (COL), as indicated. Bottom, CERKL and GFP in the various lanes using anti-Flag. <b>D</b>) COS-7 cells transfected with CERKL-HA were fixed with 2% paraformaldehyde and CERKL (HA) was localized by immunofluorescence. Images at higher magnification of the rectangles are shown on the right. Arrowheads indicate the particles containing CERKL. Bars: 10 µm (original image) and 2 µm (zoom).</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926187, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g006"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CERKL_interacts_with_microtubules_/926187", "title"=>"CERKL interacts with microtubules.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357639"], "description"=>"<p>HEK-293T cells were transfected with CERKL-WT and after 48 h a cytoskeletal fraction was isolated from the cells as described in Materials and Methods. Fractions were treated with 15 mM EDTA (<b>A</b>) or 100 µg/ml RNase A (<b>B</b>) in the presence of 150, 450 and 600 mM NaCl, as shown in the figure, and then subjected to immunoprecipitation with anti-Flag M2 affinity beads. The co-immunoprecipitated proteins were analyzed by immunoblot using antibodies that recognize eIF3B, PABP, HSP70, RPS3 and Flag (for CERKL). In the histograms below, the bands corresponding to the various proteins recovered after the Flag IP, in the presence of RNase A, were quantified with respect to CERKL-WT (<b>A</b>) or to CERKL-C125W (<b>B</b>) in each lane. Values are the mean from 4 different experiments. Stars indicate statistically significant differences from the values in the presence of 150 mM NaCl (*p<0.05, **p<0.01 and ***p<0.005).</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926188, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g007"], "stats"=>{"downloads"=>4, "page_views"=>42, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_compact_CERKL_mRNP_complexes_interact_with_microtubules_/926188", "title"=>"The compact CERKL-mRNP complexes interact with microtubules.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357642"], "description"=>"<p><b>A</b>) SH-SY5Y cells were transfected with CERKL-HA and after 48 h cells were differentiated with 10 µM retinoic acid. The distribution of CERKL and acetyl-α-tubulin were compared after 36 h by immunofluorescence. Images at higher magnification of the rectangles in the upper row are shown below. <b>B</b>–<b>D</b>) SH-SY5Y were transfected and differentiated as in <b>A</b>. Images show colocalization by immunofluorescence of CERKL (HA) with eIF3B (<b>B</b>), PABP (<b>C</b>) and RPS3 (<b>D</b>) in differentiated SH-SY5Y cells. Images at higher magnification of the rectangles in the upper row are shown below. <b>E</b>) Colocalization of CERKL-WT and CERKL-C125W (HA) with RNA (propidium iodide staining, PI) in differentiated SH-SY5Y cells. Arrowheads show colocalization in particulated structures. The scatter diagrams below show colocalization dots. Bars: 10 µm (original images) and 5 µm (zoom).</p>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926189, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.g008"], "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CERKL_localization_in_differentiated_SH_SY5Y_neural_cells_/926189", "title"=>"CERKL localization in differentiated SH-SY5Y neural cells.", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/4357594", "https://ndownloader.figshare.com/files/4357597", "https://ndownloader.figshare.com/files/4357603", "https://ndownloader.figshare.com/files/4357606", "https://ndownloader.figshare.com/files/4357609", "https://ndownloader.figshare.com/files/4357612", "https://ndownloader.figshare.com/files/4357615"], "description"=>"<div><p>The function of <i>CERKL</i> (CERamide Kinase Like), a causative gene of retinitis pigmentosa and cone-rod dystrophy, still awaits characterization. To approach its cellular role we have investigated the subcellular localization and interaction partners of the full length CERKL isoform, CERKLa of 532 amino acids, in different cell lines, including a photoreceptor-derived cell line. We demonstrate that CERKLa is a main component of compact and untranslated mRNPs and that associates with other RNP complexes such as stress granules, P-bodies and polysomes. CERKLa is a protein that binds through its N-terminus to mRNAs and interacts with other mRNA-binding proteins like eIF3B, PABP, HSP70 and RPS3. Except for eIF3B, these interactions depend on the integrity of mRNAs but not of ribosomes. Interestingly, the C125W CERKLa pathological mutant does not interact with eIF3B and is absent from these complexes. Compact mRNPs containing CERKLa also associate with microtubules and are found in neurites of neural differentiated cells. These localizations had not been reported previously for any member of the retinal disorders gene family and should be considered when investigating the pathogenic mechanisms and therapeutical approaches in these diseases.</p></div>", "links"=>[], "tags"=>["length CERKL isoform", "HSP", "disorders gene family", "eIF 3B", "approach", "localization", "Retinal Disease Gene", "mRNA", "interaction", "Compact", "C 125W CERKLa", "eIF 3B PABP", "protein", "Untranslated mRNPs Associated", "RPS", "complex"], "article_id"=>926191, "categories"=>["Biophysics", "Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Biological Sciences not elsewhere classified"], "users"=>["Alihamze Fathinajafabadi", "Eva Pérez-Jiménez", "Marina Riera", "Erwin Knecht", "Roser Gonzàlez-Duarte"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087898.s001", "https://dx.doi.org/10.1371/journal.pone.0087898.s002", "https://dx.doi.org/10.1371/journal.pone.0087898.s003", "https://dx.doi.org/10.1371/journal.pone.0087898.s004", "https://dx.doi.org/10.1371/journal.pone.0087898.s005", "https://dx.doi.org/10.1371/journal.pone.0087898.s006", "https://dx.doi.org/10.1371/journal.pone.0087898.s007"], "stats"=>{"downloads"=>11, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CERKL_a_Retinal_Disease_Gene_Encodes_an_mRNA_Binding_Protein_That_Localizes_in_Compact_and_Untranslated_mRNPs_Associated_with_Microtubules/926191", "title"=>"<i>CERKL</i>, a Retinal Disease Gene, Encodes an mRNA-Binding Protein That Localizes in Compact and Untranslated mRNPs Associated with Microtubules", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-02-03 19:21:46"}

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[282]}, {"subject_area"=>"/Biology and life sciences/Developmental biology", "average_usage"=>[285]}]}
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