Nuclear RNA surveillance, mRNA export, and non-coding RNA systems
We study how nuclear RNAs are processed, surveilled, and selectively exported, and how non-coding RNAs and R-loops shape genome organisation and stability. By defining the logic of nuclear RNA fate decisions, we aim to understand how RNA systems maintain genome integrity and contribute to disease.
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Eukaryotic genomes are pervasively transcribed, generating a large and diverse population of nuclear RNAs beyond protein-coding mRNAs. While only a small fraction of these transcripts are destined for translation, the majority consist of nuclear non-coding RNAs (ncRNAs) whose functions and regulatory roles remain incompletely understood. Many ncRNAs engage in RNA–DNA hybrid formation (R-loops) or contribute to higher-order nuclear organisation through interactions with chromatin and phase-separated compartments, processes increasingly linked to genome regulation and genome stability.
To preserve transcriptome integrity, cells deploy nuclear RNA surveillance pathways that identify and eliminate pervasively transcribed ncRNAs and incorrectly processed mRNAs, while selectively licensing properly matured mRNAs for export to the cytoplasm. How these decisions are made, and how RNA processing, surveillance, and nuclear export are coordinated at a systems level, remains poorly defined.
Our work dissects the molecular logic that governs nuclear RNA fate decisions, focusing on how RNA features, processing states, and nuclear context are integrated to determine whether a transcript is retained, degraded, or exported. By defining these regulatory principles, we aim to understand how nuclear RNA systems contribute to genome organisation, stability, and disease.
Key questions include:
- What functional roles do nuclear ncRNAs play in genome organisation, genome instability, and disease?
- How does the nuclear RNA surveillance machinery distinguish productive mRNAs from pervasively transcribed ncRNAs?
- What quality control mechanisms detect and eliminate incorrectly processed mRNAs within the nucleus?
- How are mature mRNAs recognised as export-competent and efficiently transported to the cytoplasm?