title: The type II poly(A)-binding protein PABP-2 genetically interacts with the let-7 miRNA and elicits heterochronic phenotypes in Caenorhabditis elegans.
abstract: The type II poly(A)-binding protein PABP2/PABPN1 functions in general mRNA metabolism by promoting poly(A) tail formation in mammals and flies. It also participates in poly(A) tail shortening of specific mRNAs in flies, and snoRNA biogenesis in yeast. We have identified Caenorhabditis elegans pabp-2 as a genetic interaction partner of the let-7 miRNA, a widely conserved regulator of animal stem cell fates. Depletion of PABP-2 by RNAi suppresses loss of let-7 activity, and, in let-7 wild-type animals, leads to precocious differentiation of seam cells. This is not due to an effect on let-7 biogenesis and activity, which remain unaltered. Rather, PABP-2 levels are developmentally regulated in a let-7-dependent manner. Moreover, using RNAi PABP-2 can be depleted by >80% without significantly impairing larval viability, mRNA levels or global translation. Thus, it unexpectedly appears that the bulk of PABP-2 is dispensable for general mRNA metabolism in the larva and may instead have more restricted, developmental functions. This observation may be relevant to our understanding of why the phenotypes associated with human PABP2 mutation in oculopharyngeal muscular dystrophy (OPMD) seem to selectively affect only muscle cells.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research (FMI), Maulbeerstrasse 66, WRO-1066.1.38, CH-4002 Basel, Switzerland.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Hurschler
authors.forename: David T
authors.initials: DT
authors.lastname: Harris
authors.forename: Helge
authors.initials: H
authors.lastname: Grosshans
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002459:Cell Fusion; D004268:DNA-Binding Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D039102:Poly(A)-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D034622:RNA Interference; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C095571:LIN-29 protein, C elegans; D035683:MicroRNAs; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C474488:let-7 microRNA, C elegans; C551477:pabp-2 protein, C elegans