Registration is now open for the RNA transport meeting 2018, hosted by the Forschergruppe2333! The Conference will take place from March 3rd to 6th, 2018 in Düsseldorf. It features a great line-up of invited speakers and aims to bring together various experts from a broad field of RNA biology with the goal of representing the current state of the mRNA-localization field. It’s going to be a really exciting meeting – you don’t want to miss out on that, so make sure to register soon!
Good news: A manuscript from the lab has just been accepted for publication in the RNA Journal!
We have identified the protein Sister-of-Sex-Lethal (Ssx) as a novel repressor of translation. Ssx is a paralog of the master regulator of female development in Drosophila, Sex-lethal (Sxl), that acts as a repressor of male-specific lethal-2 (msl-2) mRNA translation. It employs two distinct and mutually reinforcing blocks to translation that operate on the 5’ and 3’ untranslated regions (UTRs) of msl-2 mRNA, respectively. While 5’ UTR-mediated translational control involves an upstream open reading frame, 3’ UTR-mediated regulation strictly requires the co-repressor protein Upstream of N-ras (Unr) which is recruited to the transcript by Sxl.
Ssx and Sxl have a comparable RNA-binding specificity and both proteins can associate with Uracil-rich RNA regulatory elements present in msl-2 mRNA. Moreover, both repress translation when bound to the 5’ UTR of msl-2. However, Ssx is inactive in 3’ UTR-mediated regulation as it cannot engage the co-repressor protein Unr. The difference in activity maps to the first RNA-recognition motif (RRM) of Ssx. Conversion of three amino acids within this domain into their Sxl counterpart results in a gain-of-function and repression via the 3’ UTR, allowing detailed insights into the evolutionary origin of the two proteins and into the molecular requirements of an important translation regulatory pathway.
Find the full text here. RNA. 2017 Oct 31. pii: rna.063776.117. doi: 10.1261/rna.063776.117. [Epub ahead of print], PMID: 29089381
What a great meeting!
The International meeting of the SFB960 on ‘The Biology of RNA-Protein Complexes’ has just finished. We are all exhausted but also thrilled about the outstanding research that was presented. Four days of exciting and cutting edge science, 4 keynote lectures, almost 50 talks, 70 posters and more than 150 participants! Really a great meeting.
We want to thank all the participants for the lively discussions, the speakers for showcasing their fascinating research, the session chairs for coordinating the sessions and discussions and for making the speakers staying in time (we really had a busy schedule), and of course we want to particularly thank all the invited speakers for supporting our conference by accepting our invitation. Also, we want to acknowledge the people that helped setting up everything – the past days were quite hectic and we had many helping hands that did the work.
Thanks to all of you and we hope you all had safe travels home!
Genomic intron densities are highly variable across species, ranging from many introns per transcript in humans to fewer than one per transcript in some microbes. The extremophilic red alga, Cyanidioschyzon merolae, has taken intron reduction to an extreme, harboring only ~40 introns in its 5000-gene genome. This raises the question of whether this alga contains the canonical set of splicing machinery, which in humans comprises 5 small, nuclear RNAs and over 200 proteins.
On September 21st, Prof. Stephen D. Rader from the University of Northern British Columbia, Canada, will talk about ‘The Highly Reduced Spliceosome of C. merolae’. To study the biological role of this tiny intron complement, Stephen and his group have characterized the splicing machinery in C. merolae. Surprisingly, it is completely lacking the U1 snRNP, comprises only ~40 core proteins, has but a single LSm complex, and appears to have an RNA degradation complex associated with it.
The unexpected observation of apparent splicing regulatory proteins raised the possibility that the splicing events in C. merolae, few though they are, are regulated in response to environmental conditions or other cues. Stephen will discuss current efforts to investigate this possibility. The small size of the C. merolae spliceosome make this a promising system in which to study core features of the splicing pathway, as well as the evolutionary pressures that result in reduced splicing systems.
The sequence of the RNA is determined by the DNA template that encodes it. However, after synthesis it can be enzymatically altered. on August 31st, Dr. Konstantin Licht from the Center for Anatomy and Cell Biology of the Medicla University of Vienna from will talk about Adenosine deaminases acting on RNA (ADAR1 or ADAR2) enzymes that catalyze the conversion of Adenosine to Inosine (A-to-I editing). As Inosine is interpreted as guanosine by cellular machines A-to-I editing changes the sequence information of the RNA. This can affect the coding potential of the RNA and impacts on e.g. innate immunity and miRNA maturation. Moreover, de-regulation of editing has been linked to several pathologies including epilepsy, depression, and cancer.
Editing sites in protein-coding parts of transcripts are frequently defined by exon-intron base-pairing, and hence RNA splicing was predicted to control the extent of editing. Konstantin will present data that demonstrate that reduced splicing efficiency leads to increased editing levels when the exonic editing site is coordinated by an intron. Thus, the efficiency of splicing is of great importance for the level of editing.
Moreover, it was recently found that lethality associated with the ADAR1 knockout in mice can be rescued when proteins involved in the innate immune response (MDA5, MAVS) are also deleted. This allowed the generation of viable, editing-deficient mice (ADAR1/ADAR2 double-null mice) that were used to create the first high-confidence map of editing sites which suggest extensive cross-talk between splicing and editing.
This is going to be really exciting!
The International meeting of the SFB960 on ‘The Biology of RNA-Protein Complexes’ is just around the corner…From October 11th to 14th, there will be exciting talks about the latest research on RNPs. Keynotes will be by Allan Hinnebusch, Reinhard Lührmann, Roy Parker, and Nahum Sonenberg. Check out the rest of the program and make sure to register before August 31st – there is only a rather small number of free places left!
August 10th, 2pm in H53: An exciting lecture you should definitely not miss! Ivo Telley from the Instituto Gulbenkian de Ciência in Oeiras, Portugal, will talk about the physical principles underlying nuclear division.
In Drosophila embryos, zygotic nuclei initially undergo rapid successive divisions without cytokinesis and, therefore, a vast number of nuclei share the same intracellular space in a syncytium. They need to be evenly distributed throughout a large cytoplasmic volume and brought to the cell cortex to form even-sized cells. The regular arrangement of the nuclei is vital to later embryo development, and defects that perturb this distribution are lethal. How the regular nuclear distribution during early divisions is achieved and maintained is an interesting yet unresolved question.
One of Ivo’s main research tracks is to understand the physical principles underlying the regular arrangement and precise positioning of nuclei, and the mechanism that maintain the regularity of the nuclear distribution during perturbations such as nuclear division. He will present new insight into the mechanics of nuclear distribution and point at microtubule-based molecular interactions that are involved in distance maintenance between nuclei. It is known that the microtubule cytoskeleton plays a key role in nuclear transport, and its dynamics is greatly determined by the microtubule-organizing center, the centrosome. Ivo has evidence from mitotic mutants which suggests that the centrosomes, and not the nuclei, are the spatial organizer in the early embryo.
Finally, he will present efforts in developing an extract approach to study young fertilized eggs and visualize pronuclei and sperm in time-lapse and high-resolution, something which has not been possible before. With this approach, he aims to study how Wolbachia infection in Drosophila affects the last stages of fertilization and, in particular, what causes the first mitotic division to fail.
At the Instituto Gulbenkian de Ciência in Oeiras, Portugal, Ivo is head of a multidisciplinary research team interested in the physical aspects of intracellular organization. As a model system, they study the earliest stage of Drosophila development, from the mature egg to fertilization to pre-blastoderm cleavages. They focus on pronuclear fusion in the fertilized egg and how the syncytial embryo defines the inter-nuclear distance between rapid mitotic divisions. They employ reconstitution approaches in egg explants combined with time-lapse light microscopy and image processing while taking advantage of Drosophila genetics. By applying this assay in a study of host-micro-organism interactions, they have started to investigate how Wolbachia infection in Drosophila affects the last stages of fertilization preceding developmental arrest due to cytoplasmic incompatibility.
Did you ever go to a conference addressing a topic well outside your comfort zone? No? Well, then you are missing out on some great and exciting science!
I was recently invited to the German American Frontiers of Engineering (GAFoE) Symposium in Evendale, Ohio, by the Alexander von Humboldt Foundation. The sessions were planned to cover a great diversity of topics ranging from ‘Gene Editing’ to topics that initially sounded rather mysterious to me, like ‘Advanced Manufacturing’, ‘Industry 4.0 vs. Industrial Internet of Things’, and ‘Streams of Water and Information’. To be honest, I was puzzled about the invitation to participate. I didn’t really feel like somebody who could contribute a lot to this meeting. But then I thought why not try something new? I eventually accepted the invitation and that turned out to be a great decision!
In particular the sessions with the rather mysterious titles were the most exciting and fascinating ones to me! Everything was new and every single talk provided me with novel insights into topics that I had so far not really thought about a lot. Looking beyond one’s own nose can sure be a very stimulating and exciting experience! I feel that during this GAFoE meeting from March 31st to April 2nd, 2017, I learned more than in the previous three meetings combined.
But hearing about novel topics is one thing – it was even more exciting to meet the many other, enthusiastic participants. Most of them felt to be non-experts, too, and they were evenly excited to expand their knowledge into the other disciplines. This created a unique atmosphere and stimulated discussions that continued at the hotel bar into the early morning hours.
So, if you ever get invited to a meeting that addresses a topic that appears quite distant to your own research interests, don’t immediately turn down the invitation – rather think about the great opportunity to learn something new and meet new people.
I would like to thank the Alexander von Humboldt Foundation for the invitation and the travel stipend, the National Academy of Engineering, GE aviation for hosting us, and all the organizers for putting together such a great meeting!
Good news! We are happy to announce that our review on the function of the Drosophila RNA-binding protein Sex-lethal (Sxl) was recently accepted. Sxl is particularly interesting: it is a rather small RNA-binding protein with a simple architecture, nonetheless it engages in the regulation of multiple aspects of gene expression to direct female development. The review is open access and can be downloaded here. Let us know what you think about it!
One equals two!
While this simple statement gets most people shaking their heads in disbelief, we geneticists get all excited. It is about dosage compensation – intricate genetic programs that ensure an equal gene dose from different numbers of chromosomes.
Why is that important? Most higher eukaryotes reproduce sexually, allowing them to combine alleles from two different individuals thus increasing variability in the offspring and resulting in the cleansing of harmful mutations from a population. Sexual reproduction usually requires animals of two different sexes: males and females. Although numerous exceptions exist, the two sexes typically differ in the number of X chromosomes. However, it is critical for survival that the genetic output from different numbers of X chromosomes is matched. This poses a big challenge to gene expression. In nature several different strategies have been invented to achieve a comparable gene dose in the two different sexes by either reducing the genetic output from two X chromosomes or by boosting transcription of the single X chromosome.
Drosophila melanogaster has long served as a genetic model system to study dosage compensation in molecular detail. Female flies carry two X chromosomes (XX) and males one (XY). Dosage compensation is achieved by hypertranscription of the single, male X chromosome, essentially doubling its output. But how is this achieved on a molecular level?
On May 23rd, Peter Becker from the Ludwig-Maximilians-University in Munich will talk about how flies assemble a remarkable regulator to boost transcription of the single male X chromosome. Join us at 5p.m. in H53 for exciting science!
From March 13th-15th, the DFG Forschergruppe FOR2333 met at the EMBL in Heidelberg to discuss the latest scientific results. In parallel several workshops were offered that provided hands-on training on various exciting topics including: an introduction to structural biology (by Dierk Niessing and Fulvia Bono), an introduction to bioinformatics (by Kathi Zarnack and Markus Seiler), image analysis (Imre Gaspar), and preparation of scientific figures (by Helena Jambor).
‘During these two very exciting days I have learned a lot and had a great time being part of this wonderful meeting.’ (Rebecca Moschall)
‘A very well organized and extremely helpful course on RNA-Seq analysis featuring top-notch speakers and experts in the field’
– that is how one of the participants summarized the recent bioinformatics course on ‘Analysis of NextGen RNA-Seq data for expression profiling and protein-binding RNAs’ that took place from October 10th to 14th at the University of Regensburg. The Graduate Research Academy RNA Biology hosted several renowned experts in the field that delivered fascinating, public lectures addressing state-of-the-art methods for gene expression profiling and RNP analysis. Afterwards 18 selected participants had the opportunity for some hands-on training on actual datasets. We are happy that so many interested students from seven different universities joined us. And apparently, according to the feedback we got, for the participants the course really did make a difference:
‘with the combination of excellent speakers and target-oriented hands-on training, this one-week course increased my knowledge on current NGS tools and enabled me to analyze my own datasets’
During five intense days, a broad variety of topics was covered. These ranged from practical considerations for setting up sequencing experiments (Stefan Kirsch, Fraunhofer ITEM), Sequence alignment and quality assessment (Steve Hoffmann, Universität Leipzig and Nicholas Strieder, Universität Regensburg), pecularities of high-throughput data analysis (Rainer Spang, Universitt Regensburg), differential gene expression and alternative transcript level analyses (Simon Anders, FIMM Helsinki, Charlotte Soneson, University of Zurich and Grischa Tödt, EMBL Heidelberg) to probing of RNPs (CLIP, Markus Hafner, NIH Bethesda) and translation (Ribosomal Profiling, Jan Medenbach, Universität Regensburg).
We are extremely grateful to the instructors and tutors and would like to thank all of them for their generous support! Their help, commitment, dedication, and willingness to share knowledge made a real difference and the course a big success!
In December we will have another great talk: Elmar Wahle from the Martin-Luther Universität Halle-Wittenberg will present exciting findings regarding ‘Post-transcriptional regulation of maternal mRNA during early embryonic development: The nanos mRNA of Drosophila‘.
During the early development of animal embryos, the zygotic nucleus is not transcribed. Instead, protein synthesis is driven by maternal mRNAs that were synthesized during oocyte development and stockpiled in an inactive state. Thus, regulation of protein synthesis in early embryos is post-transcriptional. A prominent example is the nanos mRNA of Drosophila, regulation of which is essential for the formation of the anterior-posterior axis of the embryo (see also here). Synthesis of the Nanos protein is driven by small fraction of nanos mRNA that is localized at the posterior pole. The bulk of nanos mRNA is distributed uniformly throughout the embryo and is translationally repressed and decays gradually.
Elmar and his team are investigating the mechanisms controlling translational repression and degradation of the non-localized nanos mRNA. Some of the proteins that they have identified as constituents of the repressor complex are universally involved in translational repression and mRNA degradation, suggesting that their findings may have significance beyond the regulation of maternal mRNAs.
So mark your calendar and join us for exciting science on December 8th at 2p.m. in H53!
On tuesday next week, Jean Yves Roignant from the institute of Molecular Biology (IMB) in Mainz will present intriguing findings that highlight the importance of m6A RNA modification in flies.
N6-methyladenosine RNA (m6A) is a prevalent mRNA modification in vertebrates. While its functions in the regulation of posttranscriptional gene expression are beginning to be unveiled, the precise roles of m6A during development of complex organisms remain unclear. Jean-Yves and his team have carried out a comprehensive molecular and physiological characterization of the individual components of the methyltransferase complex as well as of the YTH nuclear reader protein in Drosophila melanogaster. They identified the member of the split ends protein family, Spenito, as a novel bona fide subunit of the methyltransferase complex. Furthermore, they demonstrated important roles of this complex in neuronal function and sex determination, and implicate the nuclear YT521-B as a main m6A effector in these processes. Altogether, this work substantially extends our knowledge on m6A biology, demonstrating the crucial functions of this modification in fundamental processes within the context of the whole animal.