2 Oct

From Ensembles to Single-Molecule Analysis

Mark your calendars! From October 8th to 12th the Graduate Research Academy RNA Biology of the Collaborative Research Center 960 (SFB960 – Ribosome formation: principles of RNP biogenesis and control of their function) is hosting a practical course on modern methods for the analysis of ribonucleoproteins (RNPs). Diverse topics will be covered ranging from biophysical analyses (such as isothermal calorimetry and thermophoresis), single-molecule RNP studies (single-molecule FRET and FISH), RNA structure probing and the latest RNA interactome capture methodology. In the morning, renowned experts will deliver lectures to introduce the individual topics, followed by hands-on experimentation in the afternoon. All lectures are open to the public, so even if you didn’t register, you certainly don’t want to miss out on the exciting talks by Rastislav Horos (EMBL Heidelberg), Agatha Korytowski (Malvern Panalytical GmbH), Stefanie Nunes Rosa (Swedish University of Agricultural Sciences, Uppsala), Joel Perez-Perri (EMBL Heidelberg), Bruno Sargueil (CNRS/ Paris Descartes University), and Ralf Seidel (Universität Leipzig)!

 

 

2 Sep

Understanding RNA-based Regulation in Cells

It was a particular honor to be invited for the PhD choice lecture to the conference of the Collaborative Research Center 902 – Molecular Principles of RNA-based Regulation which took place on August 29th and 30th 2018 at the Otto-Stern-Zentrum in Frankfurt am Main. The conference featured many exciting talks on diverse topics in RNA biology.

I would like to thank the PhD students very much for the invitation – it was a real pleasure to participate in the conference!

8 Jun

NEW FINDING: Purification of Cross-linked RNA-Protein Complexes by Organic Extraction

The advent of interactome capture has allowed the unbiased identification of RNA binding proteins (RBPs) dramatically expanding their number and yielding novel insights into RNA biology (see also our recent review).

For interactome capture, RBPs are photo-cross-linked to their RNA targets. Subsequently, oligo-dT resin is used to capture polyadenylated RNAs and to co-purify with them the covalently bound proteins. RNAs that lack a ploy(A)-tail can, however, not be captured by this approach, limiting its broad application. In particular, prokaryotic organisms that do not polyadenylate their mRNAs are not amenable to interactome capture.

Now three manuscripts have been uploaded to bioRxiv by the Lilley, Krijgsveld, and Beckmann labs (we contributed to one of them). In all cases extraction with organic solvents is employed to purify cross-linked RNPs (see figure) circumventing the requirement of a poly(A)-sequence for RNP capture. Moreover, this approach also captures RBPs that bind to RNA as short as 30 nt.

 

 

The manuscripts can be found here:

Purification of Cross-linked RNA-Protein Complexes by Phenol-Toluol Extraction

Unbiased dynamic characterization of RNA-protein interactions by OOPS

The Human RNA-Binding Proteome and Its Dynamics During Arsenite-Induced Translational Arrest

12 Apr

RNA Transport Meeting 2018

Organized and hosted by the DFG-funded Research Unit 2333 ‘Macromolecular complexes in mRNA localization’ (FOR2333), the RNA transport meeting 2018 took place from March 3rd to 6th in Düsseldorf. The keynote lectures by Christine Mayr and Erin Schuman were embedded in an exciting scientific program that featured talks by 18 invited speakers and by members of the FOR2333 network. For us it was a great opportunity to share and discuss our latest findings with the community.

1 Dec

Good News: Jan’s Habilitation is almost finished…

On Wednesday, November 29th, Jan successfully finished the final phase of his Habilitation by delivering a lecture in front of the entire faculty.

`I want to thank everybody who supported me along the way, in particular my lab and the colleagues in the Biochemistry I department of the University of Regensburg, especially Gunter Meister. Also without the help of our colleagues in the Collaborative Research Center 960 (Sonderforschungsbereich SFB960), our excellent collaborators, and the funding (provided by BioSysNet, DFG and BMBF) we would not have succeeded with our scientific work that was an essential part of the Habilitation.´

It is a german tradition to prepare a handcrafted hat as a present for candidates that have just obtained their doctoral degree. Jan also got a super-cool Drosophila hat for his Habilitation – thank you to everybody who helped crafting it!

29 Nov

Another manuscript accepted…

Nucleic Acids Research just accepted another manuscript for publication to which we have contributed. In an experimental effort headed by our colleague Sébastien Ferreira-Cerca (University of Regensburg, Biochemistry III), the function of the atypical Rio kinases in ribosomal smal subunit (SSU) biogenesis and maturation was addressed in Archea. This revealed activation of Rio2 by an ancient and conserved mechanism involving ribosomal RNA that stimulates release of the kinase from the nascent 40S particle. Watch out for the next NAR table of contents: there you should find a link to the manuscript, once it is out!

16 Nov

RNA transport meeting coming up…

picture courtsey of M. Feldbrügge

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!

10 Nov

Sino-German Symposium on RNA Biology

 

The second Sino-German Symposium on RNA Biology with the title `From Big Data and Structure to Novel Mechanisms´ was held in Shanghai from November 4th to 8th. It was an exceptional meeting featuring many scientific highlights!

The meeting was co-organized by the CAS-MPG Partner Institute for Computational Biology (co-established by the Chinese Academy of Sciences and the Max Planck Society) and the CAS Key Laboratory of Computational Biology. I want to thank our hosts for their outstanding hospitality and the great organization. It was a truly outstanding combination of state-of-the-art science with cultural and culinary highlights in the vibrant city of Shanghai. Xièxiè to all of you!

4 Nov

New publication from the lab

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

 

16 Oct

International SFB960 Conference on ‘The Biology of RNA-Protein Complexes’

 

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!

 

(Picture: Universität Regensburg, Referat II/2 – Kommunikation, Lilly Peithner)
15 Oct

SFB960 conference

The president of the University of Regensburg Prof. Dr. Udo Hebel (on the right) and the organizers of the SFB960 conference on  ‘The Biology of RNA-Protein Complexes (from left to right: Prof. Dr. Herbert Tschochner, Dr. Jan Medenbach, Prof. Dr. Dina Grohmann, Prof. Dr. Thomas Dresselhaus – Prof Dr. Gunter Meister missing in the picture).

28 Aug

September 21st, 2017 – Guest Speaker: Stephen Rader

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.

 

22 Aug

August 31st, 2017 – Guest Speaker: Konstantin Licht

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.

20 Aug

Conference coming up…

 

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!