2 Mar

New publication: U2AF26 and U2AF35 as regulators of translation

A function in splicing versus a function in translational control – why not both?

U2AF proteins are best known for their functions in spliceosomal processing of pre-mRNAs where a homodimer of U2AF65 and U2AF35 functions in recognition of the 3′ splice site. The smaller subunit, U2AF35, contains two zinc fingers (ZnFs). Mutations therein have recently been associated with malignant transformation. The molecular function(s) of the two domains have, however, not been studied in great detail.

A collaborative effort, spearheaded by the Heyd lab at the Free University of Berlin, now revealed that the two ZnFs have remarkably different activity. Both are required for splicing regulation, whereas only ZnF2 controls protein stability and contributes to the interaction with U2AF65.

Intriguingly, a naturally occuring splice variant of U2AF26, a paralog of U2AF35, lacks the second ZnF. It is upregulated upon activation of primary mouse T cells and localizes to the cytoplasm, suggesting a splicing-independent function. Employing ribosome profiling in a model T cell line, we provide evidence for a role of U2AF26 in activating cytoplasmic steps in gene expression, notably translation. Consistently, an MS2 tethering assay shows that cytoplasmic U2AF26/35 increases translation when localized to the 5ʹUTR of a model mRNA. This regulation is partially dependent on ZnF1 thus providing a connection between a core splicing factor, the ZnF domains and the regulation of translation. Altogether, our work reveals unexpected functions of U2AF26/35 in mammalian cells beyond the regulation of splicing.

Check out the exciting paper in RNA Biology: https://doi.org/10.1080/15476286.2020.1732701

21 Feb

February 25th, 2020 – Guest Speaker: Sebastian Leidel

tRNA modifications – Connecting translation dynamics to cellular quality control

On february 25th, 2020, at 5 p.m., Sebastian Leidel from the University of Bern will give a talk in H53. Sebastian and his lab have pioneered the use of ribosome profiling to understand the importance of tRNA modifications in translation.

tRNAs are key players in mRNA translation linking amino acids to a specific codon sequence. Interestingly, tRNA molecules carry a plethora of chemical modifications of their nucleotides, which are posttranscriptionally introduced by many different enzymatic pathways. Even though huge progress has been made, it is still unclear how most of these tRNA modifications contribute to cellular function. This is of particular importance as GWAS studies have linked different modification pathways to a number of degenerative diseases and cancer. New technologies explored by Sebastian and his lab have provided novel insights into this exciting research field.

We are looking forward to seeing you on Tuesday for an evening of exciting science!

16 Dec

New lab member: Andreas Meindl

Andreas Meindl has just joined the lab as a PhD student. Andreas will work on the function of Sex-lethal in Drosophila melanogaster sexual development addressing in detail its auto-regulatory feedback to splicing. Welcome to the lab!

2 Dec

Open position: Technical Assistant

You want to work on exciting and diverse research projects employing state-of-the-art methodologies? You want to join a young and highly motivated team? Then get your CVs ready, there is a job opening for a Technical Assistant!

The basic information: Salary TV-L E9, starting date as soon as possible, application deadline December 22nd 2019.

For more information (in German) please click here.

1 Dec

January 30th, 2020 – Guest Speaker: Florian Heyd

Some like it cold: (Body)temperature-controlled kinase activity in circadian biology, sex determination and beyond

In numerous animals (including crocodiles, alligators, tortoises, and some teleost fish), sex is determined independently of the genotype. Rather the temperature experienced during embryonic or larval stages results in the development of phenotypically male or female animals. Exemplarily, exposing alligator eggs to elevated temperatures produces mostly male offspring. The mechanism by which subtle changes in temperature are sensed to govern sex-specific development, however, has remained elusive.

On January 30th 2020 (2p.m. in H53), Florian Heyd from the Freie Universität Berlin will talk about protein kinases that act as very sensitive thermo-sensors to control changes to alternative splicing. The exciting work combines enzymology, structural-, and RNA biology to reveal in molecular detail how the activity of CDC-like kinases (CLKs) is altered by changes in temperature, resulting in differential phosphorylation of SR-proteins and subsequently in altered splicing patterns.


Click here for the advertisement of the talk.


5 Nov

SFB960 PIs in 2019

The Collaborative Research Centre 960 (SFB960) ‘RNP biogenesis: assembly of ribosomes and non-ribosomal RNPs and control of their function’ has recently been awarded funding for another four years (see this post). The 18 group leaders (pictuerd below) will head 16 research and 3 service projects and a graduate school.

We are looking forward to four more years of collaborative research and exciting new findings.

Principal Investigators third funding period (from left to right): J. Medenbach, J. Griesenbeck, T. Heise, P. Milkereit, W. Seufert, A. Bruckmann, S. Ferreira-Cerca, M. Kretz, J. Perez-Fernandez, T. Dresselhaus, G. Längst, R. Sprangers, H. Tschochner, D. Grohmann, and C. Engel;
missing on the photo: G. Sommer, S. Sprunck, G. Meister, K. Grasser

14 Oct

New lab member: Mortiz Freyberg

Today, Moritz Freyberg joined the lab for his MSc work. He already spent some time with us for an extended practical and he will now continue to work on stress-mediated gene regulation in mammalian cells. Welcome back!

11 Sep

Annual Conference of the Giessen Graduate Centre for the Life Sciences (GGL)

Last year, the PhD students of the International Giessen Graduate Centre for the Life Sciences (GGL) invited me to to deliver a keynote lecture during the annual conference. To sum up the event: I had a blast! On the one hand, it was great to return to my Alma Mater – the Justus-Liebig-Universität Giessen – for a scientifically very diverse and exciting meeting covering ten interdisciplinary research sections. On the other hand, I could catch up with old friends and colleagues many of whom I am still collaborating with.

This year, a speaker invited to deliver a keynote lecture at the conference unfortunately had to cancel on short notice. I was lucky enough to be asked to step in and present some of our recent data at the 2019 GGL conference on September 4th. Needless to say, that after the great experience last year, I agreed immediatly. And again, I very much enjoyed the conference and the scientific discussions. It was great to see the enthusiasm of the GGL students and to listen to their talks on very diverse and exciting topics.

I would like to thank the students of the ‘Protein and Nucleic Acid Interactions’ section of the GGL (and in particluar Christina Pfafenrot) very much for hosting me and the entire GGL team for the hospitality!

12 Aug

EMBO Practical Course on Measuring Translational Dynamics by Ribosome Profiling

Get motivation letters ready! Registration for the EMBO Practical Course on Measuring Translational Dynamics by Ribosome Profiling is now open. The application deadline is Febraury 9th 2020.

We are thrilled to have a great line-up of speakers and tutors including Nicholas Ingolia (University of California, Berkeley, USA), Rachel Green (Johns Hopkins University School of Medicine, Baltimore, USA), Thomas Preiss (The Australian National University, Canberra, AU), Anne Willis (University of Cambridge, UK), Marina Rodnina (Max Planck Institute for Biophysical Chemistry, Göttingen, DE), Gerben Menschaert (BIOBIX, University of Ghent, BE), and Vladimir Benes (EMBL Heidelberg). During the course, we aim to provide both insight into the theoretical background of ribosome profiling as well as practical sessions with hands-on experimentation and computational training on how to perform ribosome profiling experiments and to analyze the resulting data. We are very much looking forward to your application and to meeting you at the Advanced Training Centre at EMBL Heidelberg in May!

23 Jun

New publication: putting copy-numbers on UPR proteins

In a collaborative effort spearheaded by the Ahrends lab at the ISAS (Leibniz-Institut für Analytische Wissenschaften) in Dortmund, we established a targeted proteomics approach aimed at analyzing components of the Unfolded Protein Response (UPR), an adaptive signal transduction pathway triggered by the accumulation of unfolded proteins in the endoplasmic reticulum. The UPR comprises an important cellular stress response that aims at re-instating cellular homoeostasis and it plays a key role in a variety of disorders (including diabetes, neurodegenerative disorders, and inflammatory processes). It has also emerged as an attractive target for therapeutic intervention in cancer due to its implication in tumor progression, malignancy and resistance to therapy. The newly developed high-resolution targeted proteomics strategy combines high specificity and sensitivity, allowing the accurate quantification of UPR proteins down to the lower attomol range in a straightforward way without any prior enrichment or fractionation approaches. This has allowed us to determine cellular protein copy numbers of UPR receptors, transducers and effectors, yielding novel insights into an important cellular stress response pathway.

picture from: Nguyen et al., Scientific Reports, Volume 9, Article number: 8836 (2019) (CC BY 4.0)


Read the full manuscript at Scientific Reports: Nguyen et al. A sensitive and simple targeted proteomics approach to quantify transcription factor and membrane proteins of the unfolded protein response pathway in glioblastoma cells.

22 Jun

RNA Meeting in Krakow

The 24th annual meeting of the RNA Society took place from June 11th to 16th in the beautiful city of Krakow, Poland. It was a scientifically very stimulating conference with great talks on virtually all aspects of RNA biology. I am very happy that our abstract on how Drosophila Sister-of-Sex-lethal antagonizes Sex-lethal auto-regulatory feedback to reinforce a male-specific gene expression pattern was selected for a talk.

The conference also was the perfect opportunity to catch up with colleagues many of which have become close friends over the years – the RNA society truly has become my scientific family!



Three generations of Bindereif-lab alumni

18 Jun

Ribosome Profiling Practical Course

An EMBO practical course on Measuring Translation Dynamics by Ribosome Profiling is coming up in May 2020. Fantastic speakers are supporting the course including Nicholas Ingolia (University of California, Berkeley, USA), Rachel Green (Johns Hopkins University School of Medicine, Baltimore, USA), Thomas Preiss (The Australian National University, Canberra, AU), Anne Willis (University of Cambridge, UK), Marina Rodnina (Max Planck Institute for Biophysical Chemistry, Göttingen, DE), and Gerben Menschaert (BIOBIX, University of Ghent, BE). The Couse is organized by Sebastian Leidel, Pavel Baranov and Jan Medenbach and will include numerous lectures as well as hands-on training on how to perform ribosome profiling experiments and how to analyze the data. More information will be available soon on the EMBL courses website.

16 Jun

PhD positions available

We could successfully extend funding of the Collaborative Research Centre 960 (SFB960) ‘RNP biogenesis: assembly of ribosomal and non-ribosomal RNPs and control of their function’. To continue our ambitious research programs, we are now seeking highly motivated PhD students. We offer a highly competitive research environment and exciting research projects. For more information click here.