title: MiRNA need a TRIM regulation of miRNA activity by Trim-NHL proteins.
abstract: Trim-NHL proteins are defined by RING, B-Box and Coiled-coil protein motifs (referred to collectively as the Trim domain) coupled to an NHL domain. The C. elegans, D. melanogaster, mouse and human Trim-NHL proteins are potential and in several cases confirmed, E3 ubiquitin ligases. Current research is focused on identifying targets and pathways for Trim-NHL-mediated ubiquitination and in assessing the contribution of the NHL protein-protein interactiondomain for function and specificity. Several Trim-NHL proteins were discovered in screens for developmental genes in model organisms; mutations in one of the family members, Trim32, cause developmental disturbances in humans. In most instances, mutations that alter protein function map to the NHL domain. The NHL domain is a scaffold for the assembly of a translational repressor complex by the Brat proto-oncogene, a well-studied family member in Drosophila. The link to translational control is common to at least four Trim-NHLs that associate with miRNA pathway proteins. So far, two have been shown to repress (Mei-P26 and Lin41) and two to promote (NHL-2, Trim32) miRNA-mediated gene silencing. In this chapter we will describe structure-function relations for each of the proteins and then focus on the lessons being learned from these proteins about miRNA functions in development and in stem cell biology.
authors.affiliation: Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany. gregory.wulczyn@charite.de
authors.forename: F Gregory
authors.initials: FG
authors.lastname: Wulczyn
authors.forename: Elisa
authors.initials: E
authors.lastname: Cuevas
authors.forename: Eleonora
authors.initials: E
authors.lastname: Franzoni
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rybak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000502:physiology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; C530643:Mei-P26 protein, Drosophila; D008565:Membrane Proteins; D035683:MicroRNAs; C539315:NHL-2 protein, C elegans; D000090063:Proto-Oncogene Mas; C114030:TRAT1 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C094027:TRIM32 protein, human; D044767:Ubiquitin-Protein Ligases