title: lin28 proteins promote expression of 17∼92 family miRNAs during amphibian development.
abstract: BACKGROUND
  Lin28 proteins are post-transcriptional regulators of gene expression with multiple roles in development and the regulation of pluripotency in stem cells. Much attention has focussed on Lin28 proteins as negative regulators of let-7 miRNA biogenesis; a function that is conserved in several animal groups and in multiple processes. However, there is increasing evidence that Lin28 proteins have additional roles, distinct from regulation of let-7 abundance. We have previously demonstrated that lin28 proteins have functions associated with the regulation of early cell lineage specification in Xenopus embryos, independent of a lin28/let-7 regulatory axis. However, the nature of lin28 targets in Xenopus development remains obscure.
  
  
  RESULTS
  Here, we show that mir-17∼92 and mir-106∼363 cluster miRNAs are down-regulated in response to lin28 knockdown, and RNAs from these clusters are co-expressed with lin28 genes during germ layer specification. Mature miRNAs derived from pre-mir-363 are most sensitive to lin28 inhibition. We demonstrate that lin28a binds to the terminal loop of pre-mir-363 with an affinity similar to that of let-7, and that this high affinity interaction requires to conserved a GGAG motif.
  
  
  CONCLUSIONS
  Our data suggest a novel function for amphibian lin28 proteins as positive regulators of mir-17∼92 family miRNAs.
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Warrander
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Faas
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington York, YO10 5DD, UK.
authors.forename: Oleg
authors.initials: O
authors.lastname: Kovalevskiy
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington York, YO10 5DD, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Peters
authors.affiliation: Centre for Immunology and Infection, University of York, Heslington York, YO10 5DD, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Coles
authors.affiliation: York Structural Biology Laboratory, Department of Chemistry, University of York, Heslington York, YO10 5DD, UK.
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Antson
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Genever
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, UK.
authors.forename: Harry V
authors.initials: HV
authors.lastname: Isaacs
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics*; D005786:Gene Expression Regulation; D005855:Germ Layers / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C579731:Lin28a protein, Xenopus; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins
keywords: Xenopus; let-7; lin28; mir-106∼363; mir-17∼92; mir-363