The Critical Role of Protein Arginine Methyltransferase prmt8 in Zebrafish Embryonic and Neural Development Is Non-Redundant with Its Paralogue prmt1
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{"title"=>"The Critical Role of Protein Arginine Methyltransferase prmt8 in Zebrafish Embryonic and Neural Development Is Non-Redundant with Its Paralogue prmt1", "type"=>"journal", "authors"=>[{"first_name"=>"Yu ling", "last_name"=>"Lin", "scopus_author_id"=>"55890271000"}, {"first_name"=>"Yun Jung", "last_name"=>"Tsai", "scopus_author_id"=>"42462587400"}, {"first_name"=>"Yu Fang", "last_name"=>"Liu", "scopus_author_id"=>"36187032500"}, {"first_name"=>"Yi Chuan", "last_name"=>"Cheng", "scopus_author_id"=>"7404913989"}, {"first_name"=>"Chuan Mao", "last_name"=>"Hung", "scopus_author_id"=>"8067700000"}, {"first_name"=>"Yi Jen", "last_name"=>"Lee", "scopus_author_id"=>"55890229800"}, {"first_name"=>"Huichin", "last_name"=>"Pan", "scopus_author_id"=>"7403294608"}, {"first_name"=>"Chuan", "last_name"=>"Li", "scopus_author_id"=>"7501679196"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84874915262", "pui"=>"368507053", "pmid"=>"23554853", "issn"=>"19326203", "isbn"=>"10.1371/journal.pone.0055221", "doi"=>"10.1371/journal.pone.0055221", "sgr"=>"84874915262"}, "id"=>"625f690f-e296-3403-acf2-d301f6051f7b", "abstract"=>"Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of PRMT1 with an extra N-terminal sequence and brain-specific expression. We use zebrafish (Danio rerio) as a vertebrate model to study PRMT8 function and putative redundancy with PRMT1. The transcripts of zebrafish prmt8 were specifically expressed in adult zebrafish brain and ubiquitously expressed from zygotic to early segmentation stage before the neuronal development. Whole-mount in situ hybridization revealed ubiquitous prmt8 expression pattern during early embryonic stages, similar to that of prmt1. Knockdown of prmt8 with antisense morpholino oligonucleotide phenocopied prmt1-knockdown, with convergence/extension defects at gastrulation. Other abnormalities observed later include short body axis, curled tails, small and malformed brain and eyes. Catalytically inactive prmt8 failed to complement the morphants, indicating the importance of methyltransferase activity. Full-length prmt8 but not prmt1 cRNA can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with the N-terminus of Prmt8 can rescue the prmt8 morphants. In contrast, N-terminus- deleted but not full-length prmt8 cRNA can rescue the prmt1 morphants as efficiently as prmt1 cRNA. Abnormal brain morphologies illustrated with brain markers and loss of fluorescent neurons in a transgenic fish upon prmt8 knockdown confirm the critical roles of prmt8 in neural development. In summery, our study is the first report showing the expression and function of prmt8 in early zebrafish embryogenesis. Our results indicate that prmt8 may play important roles non-overlapping with prmt1 in embryonic and neural development depending on its specific N-terminus.", "link"=>"http://www.mendeley.com/research/critical-role-protein-arginine-methyltransferase-prmt8-zebrafish-embryonic-neural-development-nonred", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>8, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>3, "Researcher"=>2, "Student > Ph. D. Student"=>8, "Student > Master"=>3, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>13, "Design"=>1, "Veterinary Science and Veterinary Medicine"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/984996"], "description"=>"<p>(A) Comparison of the N-terminal amino acid sequences of human and zebrafish Prmt1 and Prmt8. The N-terminal amino acid sequences of human PRMT1 (H1; NP_938074.2), zebrafish Prmt1 (Z1; NP_956944.2), human PRMT8 (H8; NP_956944.2) and zebrafish Prmt8 (Z8; Q5RGQ2.2) were aligned by COBALT (<a href=\"http://www.ncbi.nlm.nih.gov/tools/cobalt/\" target=\"_blank\">http://www.ncbi.nlm.nih.gov/tools/cobalt/</a>). The amino acids encoded by different exons are marked by boxes. The grey shading shows identical amino acid sequence in the four entries. The conserved sequence in human and zebrafish PRMT8 before the PRMT1/PRMT8 conserved region are underlined. The glutamine-rich and proline/histidine-rich sequences are shown in italics. The second glycyl residue that might be myristoylated, the second methionine residue that corresponds to the third and alternative initiating methionine proposed in rat PRMT8 <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055221#pone.0055221-Kousaka1\" target=\"_blank\">[14]</a>, and the SGT at the conserved AdoMet-binding site that were mutated to AAA to make catalytic-inactive methyltransferase are highlighted. (<b>B</b>) Schematic representation of part of the zebrafish <i>prmt8</i> gene encompassing the 5’-flanking region, exon I to II including intron I. The accession number for zebrafish <i>prmt8</i> gene is Q5RGQ2.2. The region displayed comprises genome coordinates of the zebrafish chromosome 4 (in Jul. 2010 Zv9/danRer7 assembly). The potential NRSEs encompassed 21 nucleotides (10,230,373-10,230,353, and 10,229,127-10,229,107 complementary strand) were aligned by the consensus NRSE motif derived from the “core” motif (5′-NNCAGCACCNNGCACAGNNNC-3′). The red boxes show the NRSEs located within the 5′-flanking and the first intron of the <i>prmt8</i> gene. The MO1 and the MO2 binding site to pair with the <i>prmt8</i> initiating ATG and the second ATG are indicated.</p>", "links"=>[], "tags"=>["amino", "regions", "zebrafish"], "article_id"=>650481, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_N_terminal_amino_acid_sequence_and_critical_regions_in_the_5_region_of_zebrafish_prmt8_/650481", "title"=>"N-terminal amino acid sequence and critical regions in the 5’-region of zebrafish <i>prmt8</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:21:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/984997"], "description"=>"<p>(A) Expression of <i>prmt8</i> in different adult tissues was analyzed by RT-PCR. EF indicates the RT-PCR product of elongation factor. (B: brain; SP: spleen; G: gill; O: ovary; H: heart; SB: swim bladder; S: skin; E: eye; M: muscle; T: testis) (B) RT-PCR of <i>prmt8</i> RNA prepared from 0.25 hpf to 72 hpf embryos. (C) The spatial and temporal expression of <i>prmt8</i> RNA from 1 cell to 96 hpf by WISH in zebrafish embryonic development. (m: midbrain; Mhb: mid-hindbrain boundary; som: somites).</p>", "links"=>[], "tags"=>["rna", "zebrafish", "tissues"], "article_id"=>650482, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_analysis_of_prmt8_RNA_in_zebrafish_adult_tissues_and_embryos_/650482", "title"=>"Expression analysis of <i>prmt8</i> RNA in zebrafish adult tissues and embryos.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:22:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/985000"], "description"=>"<p>(A) Phenotypes of zebrafish embryos not injected (WT; wildtype), injected with control AMO (standard), or injected with 2 or 4 ng <i>prmt8</i> MO2 at 8, 24, and 48 hpf. (B) Percentage of normal, dead, or defective zebrafish embryos not injected, injected with standard AMO, <i>prmt8</i> MO2 (2, 4 and 8 ng), 2 ng of MO2 co-injected with <i>p53</i> MO, 5- mispair MO2, or 2 ng of MO2 co-injected with full-length <i>prmt8</i> cRNA. The embryos were examined at 24 hpf. Embryos with any of the gross phenotypic changes including curved tails, small and malformed brain and eyes, short yolk stalk, enlarged and swollen yolk and cardiac edema were classified as “defect”.</p>", "links"=>[], "tags"=>["zebrafish", "prmt8"], "article_id"=>650484, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phenotypes_of_zebrafish_Prmt8_morphants_/650484", "title"=>"Phenotypes of zebrafish Prmt8 morphants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:22:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/985002"], "description"=>"<p>(A) Zebrafish embryos not injected (WT), injected with control AMO (standard) or 2 ng of <i>prmt8</i> MO2 were stained with an endodermal marker <i>sox 17</i> (animal pole views) or a mesodermal marker <i>tbx6</i> (side views) at 6 hpf, and an ectodermal marker <i>otx2</i> at 7 hpf. (B) Zebrafish embryos not injected, injected with control AMO or 2 ng of <i>prmt8</i> MO2 were stained with <i>myoD</i> or <i>ntl</i> at 11 hpf (dorsal views).</p>", "links"=>[], "tags"=>["phenotypes", "gastrulation", "segmentation", "zebrafish"], "article_id"=>650486, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Defective_phenotypes_at_gastrulation_and_early_segmentation_stage_of_the_zebrafish_prmt8_morphants_/650486", "title"=>"Defective phenotypes at gastrulation and early segmentation stage of the zebrafish <i>prmt8</i> morphants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:22:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/985004"], "description"=>"<p>(A) Frequencies of normal, dead or defective embryos not injected (WT), injected with 2 ng of <i>prmt8</i> MO or <i>prmt8</i> MO with full-length <i>prmt8</i> (FL) cRNA, catalytic inactive mutant <i>prmt8</i> (CI MT) cRNA, full-length <i>prmt1</i> cRNA, <i>prmt8</i> N-terminus with full-length <i>prmt1</i> (<i>prmt8+1</i>) cRNA, N-terminus-deleted <i>prmt8</i> (ND) cRNA, or G2A mutated <i>prmt8</i> cRNA. The embryos were examined and classified as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055221#pone-0055221-g003\" target=\"_blank\">Figure 3B</a>. (B) Frequencies of different phenotypes of embryos not injected (WT), injected with 2 ng of <i>prmt1</i> MO, or <i>prmt1</i> MO with full-length (FL) <i>prmt1</i> cRNA, full-length <i>prmt8</i> cRNA, N-terminal deleted (ND) <i>prmt8</i> or <i>prmt8</i> N-terminus with full-length <i>prmt1</i> (<i>prmt8+1</i>) cRNA Injected embryos were stained with <i>ntl</i> at 10 hpf and the morphants were grouped according to the degree of shortening and widening of the notochord.</p>", "links"=>[], "tags"=>["morphants"], "article_id"=>650488, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rescue_of_prmt8_or_prmt1_morphants_with_prmt8_or_prmt1_cRNA_/650488", "title"=>"Rescue of <i>prmt8</i> or <i>prmt1</i> morphants with <i>prmt8</i> or <i>prmt1</i> cRNA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:22:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/985006"], "description"=>"<p>Zebrafish embryos (24 hpf) injected with 2 ng of <i>prmt8</i> MO2, or 2 ng of MO2 together with full-length (FL) <i>prmt8</i> cRNA, <i>prmt8</i> N-terminus with full-length <i>prmt1</i> (<i>prmt8+1</i>) cRNA, N-terminus-deleted (ND) <i>prmt8</i> cRNA, catalytically inactive mutant (CI MT) <i>prmt8</i> cRNA or G2A mutated <i>prmt8</i> cRNA, were stained with <i>otx2</i> (A; dorsal view with anterior to the top) or <i>pax2.1</i> (B; lateral view with anterior to the left). Arrows indicate aberrant expression patterns at the mid-hindbrain boundaries in morphant embryos. Dash lines indicate the relative length of the dorsoventral axis of the developing brain. (C) Typical embryos from the <i>Tg(huC::eGFP)</i> fish, images were taken by Leica DM2500 epifluorescence microscope with a DFC490 CCD camera.</p>", "links"=>[], "tags"=>["perturbed", "phenotypes"], "article_id"=>650490, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characterization_of_perturbed_brain_phenotypes_in_the_prmt8_morphants_/650490", "title"=>"Characterization of perturbed brain phenotypes in the <i>prmt8</i> morphants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-13 09:23:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/985008", "https://ndownloader.figshare.com/files/985009", "https://ndownloader.figshare.com/files/985010", "https://ndownloader.figshare.com/files/985011", "https://ndownloader.figshare.com/files/985012"], "description"=>"<div><p>Protein arginine methyltransferase (PRMT) 1 is the most conserved and widely distributed PRMT in eukaryotes. PRMT8 is a vertebrate-restricted paralogue of PRMT1 with an extra N-terminal sequence and brain-specific expression. We use zebrafish (<i>Danio rerio</i>) as a vertebrate model to study PRMT8 function and putative redundancy with PRMT1. The transcripts of zebrafish <i>prmt8</i> were specifically expressed in adult zebrafish brain and ubiquitously expressed from zygotic to early segmentation stage before the neuronal development. Whole-mount <i>in situ</i> hybridization revealed ubiquitous <i>prmt8</i> expression pattern during early embryonic stages, similar to that of <i>prmt1.</i> Knockdown of <i>prmt8</i> with antisense morpholino oligonucleotide phenocopied <i>prmt1-</i>knockdown, with convergence/extension defects at gastrulation. Other abnormalities observed later include short body axis, curled tails, small and malformed brain and eyes. Catalytically inactive <i>prmt8</i> failed to complement the morphants, indicating the importance of methyltransferase activity. Full-length <i>prmt8</i> but not <i>prmt1</i> cRNA can rescue the phenotypic changes. Nevertheless, cRNA encoding Prmt1 fused with the N-terminus of Prmt8 can rescue the <i>prmt8</i> morphants. In contrast, N-terminus- deleted but not full-length <i>prmt8</i> cRNA can rescue the <i>prmt1</i> morphants as efficiently as <i>prmt1</i> cRNA. Abnormal brain morphologies illustrated with brain markers and loss of fluorescent neurons in a transgenic fish upon <i>prmt8</i> knockdown confirm the critical roles of <i>prmt8</i> in neural development. In summery, our study is the first report showing the expression and function of <i>prmt8</i> in early zebrafish embryogenesis. Our results indicate that <i>prmt8</i> may play important roles non-overlapping with <i>prmt1</i> in embryonic and neural development depending on its specific N-terminus.</p> </div>", "links"=>[], "tags"=>["arginine", "methyltransferase", "zebrafish", "embryonic", "neural", "non-redundant", "paralogue"], "article_id"=>650491, "categories"=>["Biochemistry", "Neuroscience", "Developmental Biology"], "users"=>["Yu-ling Lin", "Yun-Jung Tsai", "Yu-Fang Liu", "Yi-Chuan Cheng", "Chuan-Mao Hung", "Yi-Jen Lee", "Huichin Pan", "Chuan Li"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055221.s001", "https://dx.doi.org/10.1371/journal.pone.0055221.s002", "https://dx.doi.org/10.1371/journal.pone.0055221.s003", "https://dx.doi.org/10.1371/journal.pone.0055221.s004", "https://dx.doi.org/10.1371/journal.pone.0055221.s005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Critical_Role_of_Protein_Arginine_Methyltransferase_prmt8_in_Zebrafish_Embryonic_and_Neural_Development_Is_Non_Redundant_with_Its_Paralogue_prmt1__/650491", "title"=>"The Critical Role of Protein Arginine Methyltransferase <em>prmt8</em> in Zebrafish Embryonic and Neural Development Is Non-Redundant with Its Paralogue <em>prmt1</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-13 09:23:32"}

PMC Usage Stats | Further Information

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Relative Metric

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