Group Stefan Ameres

Mechanism and Biology of RNA Silencing

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The Question

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.

The Approach

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 Ameres

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.

Dr. Bohr-Gasse 9
1030 Vienna
Room: 2.119

+43-1-4277-54693

Spotlights

The molecular lifecycle of microRNAs

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.

Transcriptional fingerprinting convicts malignant transcriptional states

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.

SLAMseq enables time-resolved transcriptomics

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.

RNA surveillance by uridylation-triggered decay

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.

Tailor-made microRNAs

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.

Team

Stefan Ameres
Group Leader
+43-1-4277-54693
Room: 2.119

Monika Ducka
Technician
+43-1-4277-74825
Room: 2.126

Rupert Faraway
PostDoc
+43-1-4277-74823
Room: 2.122

Julia Jankowska
PhD Student
+43-1-4277-74822
Room: 2.125

Nina Khaldieh
PhD Student
+43-1-4277-52801
Room: 2.122

Tsimafei Navalayeu
PhD Student
+43-1-4277-52801
Room: 2.125

Jan Petrílek
PhD Student
+43-1-4277-52801
Room: 2.122

Niko Popitsch
Senior PostDoc
+43-1-4277-24024
Room: 2.116

Gerald Raffl
PhD Student
+43-1-4277-74822
Room: 2.122

Annamaria Sgromo
PostDoc
+43-1-4277-74822
Room: 2.122

Aleksandr Tsarev
PhD Student
+43-1-4277-52801
Room: 2.112

Vanessa Wegert
Lab Manager
+43-1-4277-74825
Room: 2.126

Selected Publications

SLAMseq resolves the kinetics of maternal and zygotic gene expression in early zebrafish embryogenesis

2022 bioRxiv

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.

2019 MOL CELL;75(4):756-768.e7.
PMID: 31350118

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.

2018 SCIENCE
PMID: 29622725

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.

2018 Nature Methods;15(4):283-289.
PMID: 29481550

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.

2017 Nature Methods;14(12):1198-1204.
PMID: 28945705

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

2016 EMBO J;35(22)

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.

2015 MOL CELL;59(2):203-16.
PMID: 26145176

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.

2012 Nature Methods;9(4):403-9.
PMID: 22388288

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.

2010 SCIENCE;328(5985):1534-9.
PMID: 20558712

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.

2007 CELL
PMID: 17632058

Ameres, Stefan Ludwig; Martinez, Javier; Schroeder, Renée

Collaborations & Funding

European Research Council (ERC)

Project title: “Bridging temporal resolution gaps to dissect RNA silencing at the molecular and genomic scale" (ERC-CoG, RiboTrace, 866166)

National Scientific Research Fund (FWF)

SFB RNAdeco: Decorating RNA for a purpose

Project title: “Molecular origin and biological function of microRNA sequence diversification" (F8002)

National Scientific Research Fund (FWF)

doc.funds "RNA@core: Molecular mechanisms in RNA biology" (DOC177)

EMBO Young Investigator Program

Since 2017, Stefan Ameres is part of the EMBO YIP Program

Houska Award

The Ameres Lab is recipient of the Houska Award (B&C Private Foundation)

PhD and Postdoc Fellowships

Vienna BioCenter RNA Club

The Ameres Lab is part of the VBC RNA Club, sponsored by the RNA Society

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