title: Conservation of context-dependent splicing activity in distant Muscleblind homologs.
abstract: The Muscleblind (MBL) protein family is a deeply conserved family of RNA binding proteins that regulate alternative splicing, alternative polyadenylation, RNA stability and RNA localization. Their inactivation due to sequestration by expanded CUG repeats causes symptoms in the neuromuscular disease myotonic dystrophy. MBL zinc fingers are the most highly conserved portion of these proteins, and directly interact with RNA. We identified putative MBL homologs in Ciona intestinalis and Trichoplax adhaerens, and investigated their ability, as well as that of MBL homologs from human/mouse, fly and worm, to regulate alternative splicing. We found that all homologs can regulate alternative splicing in mouse cells, with some regulating over 100 events. The cis-elements through which each homolog exerts its splicing activities are likely to be highly similar to mammalian Muscleblind-like proteins (MBNLs), as suggested by motif analyses and the ability of expanded CUG repeats to inactivate homolog-mediated splicing. While regulation of specific target exons by MBL/MBNL has not been broadly conserved across these species, genes enriched for MBL/MBNL binding sites in their introns may play roles in cell adhesion, ion transport and axon guidance, among other biological pathways, suggesting a specific, conserved role for these proteins across a broad range of metazoan species.
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Oddo
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Saxena
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Ona L
authors.initials: OL
authors.lastname: McConnell
authors.affiliation: Center for Neurogenetics, University of Florida, Gainesville, FL 32610, USA Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA Department of Chemistry and Biochemistry and Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Berglund
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA eric.t.wang@ufl.edu.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Wang
mesh_terms: D000818:Animals; D002938:Ciona intestinalis / Q000378:metabolism; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D063990:Gene Ontology; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D059372:Nucleotide Motifs / Q000235:genetics; D054909:Placozoa / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins