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Gene regulation is the fundamental process that controls genome function and it pervades most biology, from organismal development to cellular differentiation and physiological responses to external stimuli and pathogens. At the post-transcriptional level, the control over RNA fate and function has emerged as a central hallmark of gene regulation with enormous biological, technological and biomedical implications. But what are the timescales, molecular features and constituting components of transcript-specific and global RNA decay? And how does post-transcriptional gene regulation intersect with dedicated pathways of RNA metabolism to support robust biological systems? Our goal is to understand how the quality and quantity of the transcriptome is controlled at the molecular level in flies and mammals.
Our studies aim to [1] provide insights into the emerging role of RNA modifications in the regulation of RNA fate and function, [2] determine possible causes for aberrant gene expression profiles that have been associated with human diseases; and [3] establish technologies that unravel the molecular signatures of RNA decay, as well as its functional components and their organization in pathways. To this end, we employ quantitative biochemical methods, cell culture experiments, and in vivo genetics to dissect the mechanisms and biological functions of RNA silencing in flies and cultured mammalian cells; and we combine time-resolved transcriptomics and functional genetics with bioinformatics, to unravel the time-scales and functional organization of post-transcriptional gene silencing at the molecular and genomic scale.
Stefan L. Ameres obtained his Master’s degree from the University Erlangen-Nuremberg (DE) and his Doctoral degree from the University of Vienna (AT). After postdoctoral training at the University of Massachusetts Medical School (US) he joined the Institute of Molecular Biotechnology (IMBA, AT) in Vienna as group leader in 2012. In 2020 he became Univ. Prof. of RNA Biology at the Max Perutz Labs.
Argonaute-bound microRNAs silence mRNA expression in a dynamic and regulated manner to control organismal development, physiology, and disease. We show that time-resolved small RNA sequencing opens new experimental avenues to deconvolute the timescales, molecular features, and regulation of small RNA silencing pathways in living cells. See our publication in Molecular Cell.
Defining direct targets of transcription factors and regulatory pathways is key to understanding their roles in physiology and disease. We combined SLAM-seq with pharmacological and chemical-genetic perturbation in order to define regulatory functions of two transcriptional hubs in cancer, BRD4 and MYC. See our publication in Science.
Gene expression profiling by high-throughput sequencing reveals qualitative and quantitative changes in RNA species at steady state but obscures the intracellular dynamics of RNA transcription, processing and decay. We show that SLAMseq facilitates the dissection of fundamental mechanisms that control gene expression in an accessible, cost-effective and scalable manner. See our publication in Nature Methods.
The posttranscriptional addition of nucleotides to the 3' end of RNA regulates the maturation, function, and stability of RNA species in all domains of life. We identified the Terminal RNA uridylation-mediated processing (TRUMP) complex that plays a key role in the cytoplasmic quality control of non-coding RNAs in Drosophila. See our publication in EMBO Journal.
Uridylation of RNA species represents an emerging theme in post-transcriptional gene regulation. In the microRNA pathway, such modifications regulate small RNA biogenesis and stability in plants, worms, and mammals. We show that hairpin uridylation may serve as a barrier for the de novo creation of microRNAs in Drosophila. See our publication in Molecular Cell.
SLAMseq resolves the kinetics of maternal and zygotic gene expression in early zebrafish embryogenesis
Bhat, Pooja; Cabrera-Quio, Luis E.; Herzog, Veronika A.; Fasching, Nina; Pauli, Andrea; Ameres, Stefan L.
Time-Resolved Small RNA Sequencing Unravels the Molecular Principles of MicroRNA Homeostasis.
Reichholf, Brian; Herzog, Veronika A; Fasching, Nina; Manzenreither, Raphael A; Sowemimo, Ivica; Ameres, Stefan L
SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.
Muhar, Matthias; Ebert, Anja; Neumann, Tobias; Umkehrer, Christian; Jude, Julian; Wieshofer, Corinna; Rescheneder, Philipp; Lipp, Jesse J; Herzog, Veronika A; Reichholf, Brian; Cisneros, David A; Hoffmann, Thomas; Schlapansky, Moritz F; Bhat, Pooja; von Haeseler, Arndt; Köcher, Thomas; Obenauf, Anna C; Popow, Johannes; Ameres, Stefan L; Zuber, Johannes
Cell-type specific sequencing of microRNAs from complex animal tissues.
Alberti, Chiara; Manzenreither, Raphael A; Sowemimo, Ivica; Burkard, Thomas R; Wang, Jingkui; Mahofsky, Katharina; Ameres, Stefan L; Cochella, Luisa
Thiol-linked alkylation of RNA to assess expression dynamics.
Herzog, Veronika A; Reichholf, Brian; Neumann, Tobias; Rescheneder, Philipp; Bhat, Pooja; Burkard, Thomas R; Wlotzka, Wiebke; von Haeseler, Arndt; Zuber, Johannes; Ameres, Stefan L
Molecular basis for cytoplasmic RNA surveillance by uridylation-triggered decay in Drosophila
Reimão-Pinto, Madalena M; Manzenreither,
Raphael A; Burkard, Thomas R; Sledz, Pawel; Jinek,
Martin; Mechtler, Karl; Ameres, Stefan L;
Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila.
Reimão-Pinto, Madalena M; Ignatova, Valentina; Burkard, Thomas R; Hung, Jui-Hung; Manzenreither, Raphael A; Sowemimo, Ivica; Herzog, Veronika A; Reichholf, Brian; Fariña-Lopez, Sara; Ameres, Stefan L
Long-term, efficient inhibition of microRNA function in mice using rAAV vectors.
Xie, Jun; Ameres, Stefan L; Friedline, Randall; Hung, Jui-Hung; Zhang, Yu; Xie, Qing; Zhong, Li; Su, Qin; He, Ran; Li, Mengxin; Li, Huapeng; Mu, Xin; Zhang, Hongwei; Broderick, Jennifer A; Kim, Jason K; Weng, Zhiping; Flotte, Terence R; Zamore, Phillip D; Gao, Guangping
Target RNA-directed trimming and tailing of small silencing RNAs.
Ameres, Stefan L; Horwich, Michael D; Hung, Jui-Hung; Xu, Jia; Ghildiyal, Megha; Weng, Zhiping; Zamore, Phillip D
Molecular basis for target RNA recognition and cleavage by human RISC.
Ameres, Stefan Ludwig; Martinez, Javier; Schroeder, Renée
Project title: “Bridging temporal resolution gaps to dissect RNA silencing at the molecular and genomic scale" (ERC-CoG, RiboTrace, 866166)
SFB RNAdeco: Decorating RNA for a purpose
Project title: “Molecular origin and biological function of microRNA sequence diversification" (F8002)
doc.funds "RNA@core: Molecular mechanisms in RNA biology" (DOC177)
Since 2017, Stefan Ameres is part of the EMBO YIP Program
The Ameres Lab is part of the VBC RNA Club, sponsored by the RNA Society
How to do proteomics better, faster, smarter - recent developments and opportunities in mass spectrometry
Biomechanics of Muscle Morphogenesis
Control of cell fate and morphogenesis in the developing brain
Activation and regulation of plant immunity by secreted signaling peptides
Transcription start site selection is environmentally controlled to diversify the proteome in eukaryotes
How evolutionary interplay between sexes can help us define phenotypes and develop drugs
Mining for protein-protein interactions with AlphaFold: Lessons from Genome Maintenance
Probing life at the nanoscale - one molecule at a time
The Underworld of Deep-Sea Hydrothermal Vents
Epigenetic regulation of germline development
Sister chromatid cohesion is mediated by individual cohesin complexes
Capturing conformational transitions in the ubiquitin conjugation cascade
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Shaping morphogen gradients: from molecules to tissues and back
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced