title: RGG boxes within the TET/FET family of RNA-binding proteins are functionally distinct.
abstract: The multi-functional TET (TAF15/EWS/TLS) or FET (FUS/EWS/TLS) protein family of higher organisms harbor a transcriptional-activation domain (EAD) and an RNA-binding domain (RBD). The transcriptional activation function is, however, only revealed in oncogenic TET-fusion proteins because in native TET proteins it is auto-repressed by RGG-boxes within the TET RBD. Auto-repression is suggested to involve direct cation-pi interactions between multiple Arg residues within RGG boxes and EAD aromatics. Via analysis of TET transcriptional activity in different organisms, we report herein that repression is not autonomous but instead requires additional trans-acting factors. This finding is not supportive of a proposed model whereby repression occurs via a simple intramolecular EAD/RGG-box interaction. We also show that RGG-boxes present within reiterated YGGDRGG repeats that are unique to TAF15, are defective for repression due to the conserved Asp residue. Thus, RGG boxes within TET proteins can be functionally distinguished. While our results show that YGGDRGG repeats are not involved in TAF15 auto-repression, their remarkable number and conservation strongly suggest that they may confer specialized properties to TAF15 and thus contribute to functional differentiation within the TET/FET protein family.
authors.affiliation: a Division of Life Science , The Hong Kong University of Science & Technology, Clear Water Bay , Kowloon , Hong Kong S.A.R. , China.
authors.forename: Bess Ling
authors.initials: BL
authors.lastname: Chau
authors.affiliation: a Division of Life Science , The Hong Kong University of Science & Technology, Clear Water Bay , Kowloon , Hong Kong S.A.R. , China.
authors.forename: King Pan
authors.initials: KP
authors.lastname: Ng
authors.affiliation: a Division of Life Science , The Hong Kong University of Science & Technology, Clear Water Bay , Kowloon , Hong Kong S.A.R. , China.
authors.forename: Kim K C
authors.initials: KK
authors.lastname: Li
authors.affiliation: a Division of Life Science , The Hong Kong University of Science & Technology, Clear Water Bay , Kowloon , Hong Kong S.A.R. , China.
authors.forename: Kevin A W
authors.initials: KA
authors.lastname: Lee
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D015870:Gene Expression; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D034802:RNA-Binding Protein EWS / Q000737:chemistry / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000737:chemistry / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators
keywords: RGG box; RNA-binding proteins; TET/FET protein family; oncoproteins; transcriptional repression