Speaker Information for:

Stefan Ameres, IMBA - Institute of Molecular Biotechnology, Vienna

Title:

Time-resolved small RNA sequencing unravels the molecular principles of microRNA homeostasis

Abstract:

Argonaute-bound microRNAs silence mRNA expression in a dynamic and regulated manner to control organismal development, physiology, and disease. We employed metabolic small RNA sequencing for a comprehensive view on intracellular microRNA kinetics in Drosophila. Based on absolute rate of biogenesis and decay, microRNAs rank among the fastest produced and longest-lived cellular transcripts, disposing up to 105 copies per cell at steady-state. Mature microRNAs are produced within minutes, revealing tight intracellular coupling of biogenesis that is selectively disrupted by pre-miRNA-uridylation. Control over Argonaute protein homeostasis generates a kinetic bottleneck that cooperates with non-coding RNA surveillance to ensure faithful microRNA loading. Finally, regulated small RNA decay enables the selective rapid turnover of Ago1-bound microRNAs, but not of Ago2-bound small interfering RNAs (siRNAs), reflecting key differences in the robustness of small RNA silencing pathways. 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.

Bio:

Stefan L. Ameres earned his Master’s degree in Biology at the Friedrich-Alexander University Erlangen-Nuremberg (Germany), and his PhD degree at the University of Vienna (Austria). In his PhD thesis, he reported the first in-depth enzymatic characterization of the human RNA interference effector complex. During his postdoctoral studies at UMass Medical School (USA), he discovered a novel pathway for the sequence-specific destruction of microRNAs in flies and mammals, establishing a potential therapeutic approach for microRNA-related diseases.  In 2012 he joined IMBA (Vienna, Austria) as a group leader, where his lab uses innovative transcriptomics to study fundamental biological mechanisms of gene regulation.

Link to website:

https://www.imba.oeaw.ac.at/research/stefan-ameres/