Research
Argonautes and their Life Cycle
Argonaute proteins are the central effectors of RNA silencing. They bind small guide RNAs and use them to recognize target transcripts, thereby controlling gene expression with sequence specificity. We study the complete Argonaute/RISC life cycle — from Argonaute activation and small RNA loading, through guide-strand selection and target silencing, to Argonaute recycling, quality control and degradation.
A major focus of our work is how Argonaute is opened and loaded with small RNAs. This process can be driven by Dicer-associated loading complexes or by HSP70/HSP90 chaperone systems. We also investigate how loaded and empty Argonaute proteins are distinguished in the cell, and how Argonaute turnover controls the capacity and fidelity of RNA silencing.
Dicer as an RNA Processing Machine
Dicer is a multidomain RNA-processing enzyme that converts double-stranded RNA precursors into small RNAs, including miRNAs and siRNAs. These small RNAs are then transferred to Argonaute proteins to initiate RNA silencing. We study how Dicer recognizes authentic RNA substrates, positions them for precise cleavage, and coordinates processing with downstream RISC assembly.
Our work focuses on Dicer as a dynamic molecular machine. We investigate how conformational changes, RNA-binding domains, intrinsically disordered regions and partner proteins such as TRBP regulate substrate selection, catalytic activity, product release and communication with Argonaute. This allows us to understand how Dicer achieves high fidelity in small RNA biogenesis while remaining adaptable across different RNA silencing pathways.
Transcription and CTD-driven regulation
The C-terminal domain (CTD) of RNA Polymerase II serves as a dynamic and adaptable platform that coordinates transcription with RNA processing. Its repetitive sequence, combinatorial phosphorylation patterns, and intrinsic disorder enable the recruitment of diverse regulatory factors.
We investigate how CTD sequence features, post-translational modifications, and phase separation properties control the spatial and temporal organization of transcription-associated machinery.
