From March 3rd to 6th 2018 our RNA transport meeting took place in Düsseldorf-Kaiserswerth, where various experts from a broad field of RNA biology were representing the current state of the mRNA-localization field.
It was a very exciting congress with outstanding keynote lectures and 9 sessions packed with excellent talks. Of course, we also had lots of fun!
At the cellular level, learning and memory rely on the physical modification of synapses, which are ultimately encoded by transported mRNAs and protein synthesis “onsite”. In previous studies, Michael Kiebler and his team have shown that the RNA-binding protein Staufen2 is essential in conveying mRNAs to their destinations. Now, a new study carried out by the Kiebler group and colleagues shows that reduced levels of Staufen2 are associated with a specific impairment of memory. Using a genetic model in which Staufen2 can be conditionally and selectively suppressed in nerve cells in the rat forebrain, they observed that Staufen2 depletion affected nerve-cell morphology, synaptic function and impaired spatial, temporal and associative memory. The findings appear in the journal Genome Biology.
Stefan M. Berger, Iván Fernández-Lamo, Kai Schönig, Sandra M. Fernández Moya, Janina Ehses, Rico Schieweck, Stefano Clementi, Thomas Enkel, Sascha Grothe, Oliver von Bohlen und Halbach, Inmaculada Segura, José María Delgado-García, Agnès Gruart, Michael A. Kiebler and Dusan Bartsch.
Forebrain-specific, conditional silencing of Staufen2 alters synaptic plasticity, learning and memory in rats.
Genome Biology 2017 Nov 17;18(1):222. doi: 10.1186/s13059-017-1350-8.
The Niessing, Jansen and Feldbrügge labs published a review on recent advances in mRNA localization in different fungal species. The review appeared in WIREs RNA and puts a special focus on the comparison of membrane-free and membrane-bound RNA transport.
Niessing, Jansen, Pohlmann & Feldbrügge
mRNA transport in fungal top models
WIREs RNA DOI: 10.1002/wrna.1453 (2017)
You can find a wrap-up of this article on the website of [Advanced Science News].
This time our regular network meeting took place in the cozy town of Tübingen in the middle of Baden-Württemberg. It was a wonderful get-together and a great opportunity to discuss the latest scientific results in RNA localization.
Thanks to Ralf-Peter Jansen and Fulvia Bono for organizing this wonderful meeting!
Lab members of the FOR2333 network participated in the EMBO conference “RNA localisation and local translation” in Barga, Italy. The conference took place from July 23rd to 28th 2017 at the beautiful Il Ciocco Resort in Tuscany and was packed with great talks and exciting science. Thanks to the organisers for this wonderful meeting!
In particular in highly polarized cells like fungal hyphal early endosomes carry out two distinct functions. Firstly, during endocytosis they function as transport unit to deliver cargo towards the lysosome/vacuole. Secondly, the same early endosomes are used to deliver cargo like mRNAs, associated ribosomes as well as protein complexes over long distances to ensure efficient polar growth. Studying the evolutionarily conserved protein Did2 revealed that this ESCRT regulator is needed to coordinate these two seemingly independent functions. This has implications for the role of early endosomes in other trafficking processes like during neuronal mRNA transport.
Haag, C., Pohlmann, T., Feldbrügge, M.
The ESCRT regulator Did2 maintains the balance between long-distance endosomal transport and endocytic trafficking.
PLoS Genet 13(4): e1006734 (2017).
From March 13.-15. 2017 the FOR2333 team held a three-days methods workshop at the Advanced Training Centre of the EMBL Heidelberg.
Students of participating groups attended training sessions on “bioinformatics”, “professional preparation of scientific figures”, “introduction to structural biology”, and “high-resolution imaging and image processing”. The sessions consisted of lectures and hands-on training, and were
designed to support students and postdocs in their own project.
Read more ›
In this study, the Ephrussi lab shows that an atypical tropomyosin isoform is a direct (m)RNA binding protein that binds preferentially to the dimerizing oskar 3’ UTR and is a component of the transported oskar mRNPs within the female germ-line. In the absence of this tropomyosin isoform, Khc fails to get loaded onto oskar mRNA, which explains the reduced motility and ultimately the failure in oskar localization. This Tm1-I/C dependent recruitment is rather inefficient – only a small fraction of oskar mRNPs acquire Khc – but dynamic, enabling the posterior-ward transport of virtually all oskar mRNPs. Most importantly, however, the Tm1-I/C recruited Khc is inactive. Activation of the motor only commences in the oocyte during mid-oogenesis – possibly to prevent interference with the other transporter of oskar, cytoplasmic dynein – and requires the previously identified exon junction complex (EJC) and associated spliced oskar localization element (SOLE).
Gaspar, I., Sysoev, V., Komissarov, A. and Ephrussi, A. (2016)
An RNA-binding atypical tropomyosin recruits kinesin-1 dynamically to oskar mRNPs.
EMBO J. DOI 10.15252/embj.201696038
In collaboration with Jernej Ule’s group at the Francis Crick Institute in London, UK, the Zarnack lab explores how different experimental steps can constrain the identification of RBP binding sites in CLIP experiments. To this end, they analysed publicly available and newly generated data for the RBPs PTBP1, eIF4A3 and U2AF65 that were produced with multiple different CLIP protocols, including iCLIP, eCLIP and irCLIP. Based on these comparisons, they present experimental considerations and computational approaches to enable an accurate identification of RBP crosslink sites.
Haberman N, Huppertz I, Attig J, König J, Wang Z, Hauer C, Hentze MW, Kulozik AE, Le Hir H, Curk T, Sibley CR, Zarnack K$, Ule J$
($ shared correspondence)
Insights into the design and interpretation of iCLIP experiments
Genome Biology (2017) 18:7. doi: 10.1186/s13059-016-1130-x
In this study the Niessing lab solved three X-ray structures to understand how the E3 localization element of the ASH1 mRNA is folded, how it is recognized in the nucleus by She2p, and how highly specific binding in the cytoplasmic is achieved by the additional joining of the myosin adapter She3p. Quite unexpectedly, the E3 element undergoes major rearrangements upon She2p binding. Furthermore, high RNA specificity in the cytoplasm is achieved through unstructured regions of She3p that introduce steric constraints. This work was performed in close collaboration with the Jansen lab of the FOR2333 team.
Edelmann FT, Schlundt A, Heym RG, Jenner A, Niedner-Boblenz A, Syed MI, Paillart J-C, Stehle R, Janowski R, Sattler M, Jansen R-P, Niessing D
Molecular architecture and dynamics of ASH1 mRNA recognition by its mRNA-transport complex
Nature Structural & Molecular Biology (2017) doi:10.1038/nsmb.3351