Transcriptome-wide view of endosomal mRNP transport reveals novel link to mitochondrial biology Lilli Olgeiser1, Carl Haag1, Susan Boerner2, Jernej Ule3, Anke Busch4, Julian König4, Michael Feldbrügge1* and Kathi Zarnack2* 1Heinrich Heine University Düsseldorf, Institute for Microbiology, Cluster of Excellence on Plant Sciences, 40204 Düsseldorf, Germany; 2Buchmann Institute for Molecular Life Sciences University Frankfurt, Riedberg Campus, Max-von-Laue-Str. 15, 60438 Frankfurt am Main, Germany; 3Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N3BG, UK; 4Institute of Molecular Biology gGmbH, Ackermannweg 4, 55128 Mainz, Germany * Joint Corresponding Authors
Active transport and local translation of mRNAs mediates spatiotemporal protein expression. Key factors of the transport machinery are RNA-binding proteins (RBPs) that recognise mRNAs as cargo for motor-based transport. However, a global view of transported mRNAs with cognate RBP-binding sites is missing. Here, we cast a transcriptome-wide view on endosomal mRNP transport in Ustilago maydis by studying the newly identified endosomal RBP Grp1 and the key transport RBP Rrm4 in a comparative iCLIP approach. This uncovered thousands of cargo mRNAs bound by both RBPs. Strikingly, Rrm4 recognises distinct landmark sites of translation, such as start and stop codons as well as the 3´ UTR, suggesting an intimate connection of transport and translation. The characteristic binding pattern allowed the classification of distinct targets sets. For example, the vast majority of mRNAs encoding subunits of the mitochondrial F0F1-ATPase are bound at the stop codon suggesting a link between translational termination and mitochondrial protein import. Altogether, we hypothesise that Rrm4 enables tailor-made transport for distinct target transcripts to synchronise translation and transport. Importantly, we discovered a novel link between endosomal mRNA transport and mitochondrial biology.
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