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SPP1935 -- Deciphering the mRNP code :
RNA-bound Determinants of Post-transcriptional Gene Regulation

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laboratoriesProf. Dr. Hüttelmaier

Stefan Hüttelmaier Center
Martin Luther University Halle-Wittenberg Institute of Molecular Medicine, Division for Molecular C

Heinrich-Damerow-Str. 1 06120 Halle


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RNA-binding proteins and post-transcriptional control of gene expression. Proteomics and function of mRNPs and ncRNPs. The role of RBPs in metabolism and cancer


The regulation of mRNA fate is essentially controlled by the interplay of mRNA-binding proteins (mRBPs) and trans-acting noncoding RNAs including microRNAs and lncRNAs (long noncoding RNAs). In the cytoplasm, the regulation of mRNA translation and turnover is largely regulated via mRNPs comprising mRNA-specific mRBP-assemblies.

In recent studies, we identified that various mRBPs associate with noncoding Y RNAs. The Y3** promotes the 3’-end processing of replication dependent histone pre-mRNA by modulating the assembly of CPSF-associated complexes and their delivery to histone locus bodies (HLBs), the site of histone mRNA synthesis and 3’-end processing. In contrast to Y3**, Y1 as well as Y3 are mainly cytoplasmic. Both Y RNAs associate with various mRBPs in Y RNPs comprising mRBPs largely associating via the single-stranded loop of Y RNAs, Ro60 binding at the stem and La associating via a polyU-rich stretch at Y RNAs’ 3’-end. We propose that Y RNPs are essential modulators of mRNP assembly controlling the subcellular sorting of mRBPs, their turnover, post-translational modification and/or complex formation. Accordingly, Y RNPs are expected to modulate the cytoplasmic fate of mRNAs and thus the post-transcriptional control of gene expression by scaffolding, sequestering and/or chaperoning mRBPs. This proposal aims at deciphering the molecular mechanisms underlying Y RNP-directed regulation of mRNP/mRBP function by focusing on the following aspects: 1) Characterization and validation of the Y RNA protein-interactome; 2) The role of Y RNAs in modulating the mRNP-association of mRBPs; 3) The role of Y RNAs in modulating subcellular sorting of mRBPs; 4) The role of Y RNAs in modulating mRBP protein turnover and modification; 5) The role of Y RNAs in controlling mRBP-directed control of cytoplasmic mRNA fate.

We expect that the proposed studies will reveal important insights into the regulation of mRBP/mRNP function, in particular in cancer-derived cells. In the latter, upregulated expression of Y RNAs, in particular Y1 and Y3 along with several mRBPs has been reported. Accordingly, the proposed studies will set the stage for evaluating the role of Y RNA-controlled mRBP/mRNP function in cancer.


- Purification of RNPs (RNA pulldown, immunopurification, density gradient centrifugation)
- Imaging technologies (live cell microscopy, photoconvertable fluorescence)
- Gene expression profiling by NGS technologies

PublicationsPUBLICATIONS :

Hüttelmaier S., Zenklusen D., Lederer M., Dictenberg J, Lorenz M, Meng X., Bassell G., Condeelis J., Singer RH*. Spatial regulation of b-actin translation by Src-dependent phosphorylation of ZBP1. Nature, 2005 Nov., Vol. 438: 512-515.

Köhn M, Lederer M, Wächter K, Hüttelmaier S. Near-infrared (NIR) dye-labeled RNAs identify binding of ZBP1 to the noncoding Y3-RNA. RNA. 2010 Jul;16(7):1420-8.

Köhn M, Pazaitis N, Hüttelmaier S. Why Y RNAs? About Versatile RNAs and Their Functions. Biomolecules. 2013; 3(1):143-156.

Wächter K, Köhn M, Stöhr N, Hüttelmaier S. Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains. Biol Chem. 2013 Aug;394(8):1077-90.

Köhn M, Ihling C, Sinz A, Krohn K, Hüttelmaier S. The Y3** ncRNA promotes the 3’-end processing of histone mRNAs. Genes and Development 2015; in press