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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  provide insights into the emerging role of RNA modifications in the regulation of RNA fate and function,  determine possible causes for aberrant gene expression profiles that have been associated with human diseases; and  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.
Structure-function analysis of microRNA 3'-end trimming by Nibbler.
Xie, Wei; Sowemimo, Ivica; Hayashi, Rippei; Wang, Juncheng; Burkard, Thomas R; Brennecke, Julius; Ameres, Stefan L; Patel, Dinshaw J
Molecular basis for target RNA recognition and cleavage by human RISC.
Ameres, Stefan Ludwig; Martinez, Javier; Schroeder, Renée