title: Zebrafish Rnf111 is encoded by multiple transcripts and is required for epiboly progression and prechordal plate development.
abstract: Arkadia (also known as RING finger 111) encodes a nuclear E3 ubiquitin ligase that targets intracellular effectors and modulators of TGFβ/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. In the mouse, loss of Arkadia results in early embryonic lethality, with defects attributed to compromised Nodal signaling. Here, we report the isolation of zebrafish arkadia/rnf111, which is represented by 5 transcript variants. arkadia/rnf111 is broadly expressed during the blastula and gastrula stages, with eventual enrichment in the anterior mesendoderm, including the prechordal plate. Morpholino knockdown experiments reveal an unexpected role for Arkadia/Rnf111 in both early blastula organization and epiboly progression. Using a splice junction morpholino, we present additional evidence that arkadia/rnf111 transcript variants containing a 3' alternative exon are specifically required for epiboly progression in the late gastrula. This result suggests that arkadia/rnf111 transcript variants encode functionally relevant protein isoforms that provide additional intracellular flexibility and regulation to the Nodal signaling pathway.
authors.affiliation: Institute of Medical Biology, Agency for Science, Technology and Research (A⁎STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Bessarab
authors.affiliation: Genome Institute of Singapore, Agency for Science, Technology and Research (A⁎STAR), 60 Biopolis Street, #02-01 Genome, Singapore 138672, Singapore.
authors.forename: Sinnakaruppan
authors.initials: S
authors.lastname: Mathavan
authors.affiliation: Institute of Medical Biology, Agency for Science, Technology and Research (A⁎STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Jones
authors.affiliation: Institute of Medical Biology, Agency for Science, Technology and Research (A⁎STAR), 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore. Electronic address: ray.dunn@imb.a-star.edu.sg.
authors.forename: N
authors.initials: N
authors.lastname: Ray Dunn
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D005775:Gastrula / Q000254:growth & development; D006801:Humans; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D055456:Nodal Signaling Ligands / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics* / Q000302:isolation & purification; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development
chemical_list: D055456:Nodal Signaling Ligands; D020033:Protein Isoforms; C427283:Rnf111 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Alternative splicing; Epiboly; Evolutionary conservation; Prechordal plate; Zebrafish; rnf111