SPP 1935:  Deciphering the mRNP code: RNA-bound determinants of post-transcriptional gene regulation

• Subject Area: Biology
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 273941853

Messenger RNAs (mRNAs) interact with trans-acting factors, including proteins and various non-coding RNAs, at all stages of their life. Since there are many mRNA-interacting factors and each mRNA encodes a particular protein, the resulting ribonucleoprotein particle (mRNPs) is unique in its composition. The composition of each mRNP is important because this 'mRNP code' is believed to control the fate and function of each individual mRNA in every cell. As many of the mRNP-associated factors become recruited, re-organised and released according to specific needs in the mRNA's life cycle, the code is highly dynamic and reflects the functional status of each mRNA.It is the goal of this Priority Programme to 'decipher the mRNP code' of eukaryotes. We aim to achieve this goal by bringing together researchers from disciplines as diverse as systems biology, biochemistry, structural biology and bioinformatics to develop and apply methods allowing insight into the composition of mRNPs, how they are assembled and remodelled and how they function in specific cellular settings of gene expression. Projects to be funded within this programme include: - the systematic identification of binding sites of mRNA-binding proteins (mRBPs) and high throughput analysis of mRNP complexes to study the formation and function(s) of mRNPs - the analysis of mechanistic and functional aspects of mRNP assembly, remodelling and disassembly - the analysis of mRNA binding protein function during gene expression within the context of a complex mRNP, and - the development of new techniques enabling mRNP analysisIdeally, more than one of the abovementioned research directions are covered in the proposed projects. PIs are also expected to have previous experience in the field of mRNP analysis.The highly demanding analysis of mRNPs often requires collaborative projects to tackle complex biological questions or to analyse large amounts of data. We therefore encourage researchers to submit tandem/interdisciplinary project with PIs from different but complementary disciplines. Such projects could combine for example bioinformatics and systems biology or biochemistry, structural biology and functional biochemistry etc. Projects addressing the following topics will not be funded:- the analysis of the functions of non-coding RNPs, such as lncRNPs, snRNPs or ribosomes if these do not involve an analysis of mRNA- projects aimed at solving structures of RBPs or RNPs without additional functional analysis- studies investigating gene expression without a clear involvement of RBPs- studies of prokaryotic or viral mRNPs

• DFG Programme: Priority Programmes

Projects

• Axonal mRNP alterations in spinal muscular atrophy (Applicants Briese, Michael ;  Sendtner, Michael A. )
• beta-propeller domains as novel RNA-binding modules (Applicant Meister, Gunter )
• Characterization of factors and mechanisms of starvation-induced control of TOP mRNA translation (Applicants Fischer, Utz ;  Vogel, Jörg )
• Control of mRNA-binding protein (mRBP) and mRNP function by Y RNAs (Applicant Hüttelmaier, Stefan )
• Control of mRNA fate by mRNP acetylation (Applicants Ohler, Uwe ;  Stoecklin, Georg )
• Coordination Funds (Applicant Gehring, Niels H. )
• Coordination project (Applicant Fischer, Utz )
• Deciphering human nonsense-mediated mRNA decay (NMD) (Applicants Dieterich, Christoph ;  Gehring, Niels H. )
• Deciphering the mRNP at premature termination codons (Applicant Neu-Yilik, Gabriele )
• Deciphering the mRNP Code for Successful Glia to Neuron Reprogramming (Applicants Kiebler, Michael ;  Ninkovic, Jovica )
• Deciphering the roles of neurite-targeted RBPs in mRNA localization and local translation (Applicants Chekulaeva, Marina ;  Selbach, Matthias )
• Deciphering the translational landscape of Arabidopsis and maize meiocytes (Applicant Schnittger, Arp )
• Differential protein- and RNA-interactions of Roquin specify alternative modes of post-transcriptional gene regulation (Applicants Heissmeyer, Vigo ;  Niessing, Dierk )
• Formation of the repressed nanos mRNP in the early Drosophila embryo (Applicant Wahle, Elmar )
• Functional analysis of kinesin-associated RNA transport granules in neurons (Applicants Kindler, Stefan ;  Kreienkamp, Hans-Jürgen )
• Functional characterization of the mRNA-binding protein ZC3HAV1 in stem cell renewal and differentiation (Applicants Landthaler, Markus ;  Rajewsky, Nikolaus )
• High-resolution mapping and quantitative modeling of cooperative RNA binding in mRNPs (Applicant Cramer, Patrick )
• Identification and functional analysis of RNA-binding sites in proteins involved in nuclear mRNP assembly in S. cerevisiae (Applicants Sträßer, Katja ;  Urlaub, Henning )
• Identification of RNA-binding proteins in macrophages by interactome capture (Applicant Ostareck-Lederer, Antje )
• Investigating early messenger ribonucleoprotein complex remodelling with RNA interactome capture (Applicant Kilchert, Cornelia )
• Investigation of the molecular mechanisms and interplay of TTP-mediated mRNA decay and translational repression using structural and biochemical tools (Applicant Chakrabarti, Ph.D., Sutapa )
• Mechanistic and functional characterization of Makorin 1 mRNPs (Applicants König, Ph.D., Julian ;  Roignant, Jean-Yves ;  Zarnack, Katharina )
• mRNP assembly at the 3' splice site studied by functional genomics and structural biology (Applicants König, Ph.D., Julian ;  Sattler, Michael )
• PCF11-dependent regulation of transcriptome 3’end mRNP dynamics during neuronal development (Applicant Danckwardt, Sven )
• Rapid ribonucleoprotein-dependent recruitment of mRNA to ribosomes in the high light acclimation of Arabidopsis thaliana (Applicant Dietz, Karl-Josef )
• Recursive splicing and mRNA polyadenylation regulatory circuits govern homeostasis and cell cycle potency of pluripotent cells. (Applicant Papantonis, Argyris )
• RNA-protein interactomics to read the yeast mRNP code (Applicant Butter, Falk )
• Structure-function analysis of a novel, maternally provided, multi-functional RNP complex in C. elegans (Applicant Ketting, Ph.D., René )
• Targets and functions of the chloroplast ribonucleoproteins CP33A and CP33B (Applicant Schmitz-Linneweber, Christian )
• The multidomain RNA-binding protein IMP3: combinatorial RNA recognition and functions during mRNP biogenesis (Applicant Bindereif, Albrecht )
• Tropomyosin 1 and End-binding protein 1 in mRNA transport (Applicants Ephrussi, Ph.D., Anne ;  Hennig, Janosch )
• Understanding the molecular interactions and mechanisms of the RNA helicase DDX6 in posttranscriptional regulation (Applicants Landthaler, Markus ;  Rajewsky, Nikolaus )

• Spokesperson: Professor Dr. Niels H. Gehring