Selective interactions of hnRNP M isoforms with the TET proteins TAF15 and TLS/FUS.
The molecular composition of macromolecular assemblies engaged in transcription and splicing influences biogenesis of mRNA transcripts. Preference for one over the other interactive protein partner within those complexes is expected to change the gene expression pattern and to affect subsequent cellular events. We report here the novel and selective associations between RNA-binding proteins, namely the hnRNP M1-4 isoforms-involved in early spliceosome assembly and alternative splicing-and the transcription factors TAF15 and TLS/FUS. In immunoprecipitation studies on HeLa nuclear extracts, TAF15 co-immunoprecipitates preferably with the higher molecular weight hnRNP M3/4 isoforms, opposite to TLS/FUS that associates with the lower molecular weight hnRNP M1/2 species. We demonstrate that these associations can be mediated through direct protein-protein interactions via the amino-termini of the TET proteins, independently of RNA. Finally, we show partial co-localization of TAF15 and TLS/FUS with hnRNP M proteins in HeLa nuclei, supporting the biochemically obtained data. The participation of hnRNP M in an expanding network of protein-protein interactions suggests its important functioning in the coordination of transcriptional and post-transcriptional events.
Medical Faculty, Institute for Biochemistry I, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany, marija.marko@uni-koeln.de.
Marija
M
Marko
Michael
M
Leichter
Meropi
M
Patrinou-Georgoula
Apostolia
A
Guialis
D006367:HeLa Cells; D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D021381:Protein Transport; D012326:RNA Splicing / Q000502:physiology; D034702:RNA-Binding Protein FUS / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry / Q000378:metabolism*
D034761:Heterogeneous-Nuclear Ribonucleoprotein Group M; D020033:Protein Isoforms; D034702:RNA-Binding Protein FUS; D011994:Recombinant Proteins; C102041:TAF15 protein, human; D035381:TATA-Binding Protein Associated Factors