Publications
2026
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Toward Mapping Spatiotemporally Resolved Transcriptomes and RNA-Protein Interactions
RNAs navigate highly regulated life cycles that include synthesis, processing, ribonucleoprotein complex formation, localization, and degradation. However, most transcriptome-wide methods capture static, cell-wide averages that obscure the spatiotemporal aspects-where and when-of RNA life. Here we review recent advances that bring spatial and temporal resolution to transcriptome and RNA-protein interaction analyses by labeling RNA either in defined subcellular locales (RNA proximity labeling) or... -
Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection
MDA5 is an innate immune RNA sensor that senses infection with a range of viruses and other pathogens. MDA5's RNA agonists are not well defined. Here we used single-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) to study its ligands. Of note, upon infection with SARS-CoV-2 or encephalomyocarditis virus, MDA5 bound overwhelmingly to cellular RNAs. Many binding sites were intronic and proximal to Alu elements and to potentially base-paired structures. Concomitantly, cytoplasmic... -
RNA signaling in cellular plasticity during homeostasis and regeneration
Cells and tissues constantly read and broadcast information through RNA. This mini-review explores how endogenous and damage-released RNAs act as instructive signals that rewire cell identity during steady-state homeostasis and injury repair. We will cover how repetitive-element-derived RNAs and regulatory long-noncoding RNAs (lncRNAs) tune stem and progenitor plasticity in hematopoietic, pluripotent, and muscle systems by coupling stress sensing to cell-fate decisions. We will also outline... -
Interplay between RNA-protein interactions and RNA structures in gene regulation
Cellular RNAs are not linear single-stranded stretches of nucleic acids as depicted in textbook cartoons but fold into secondary and tertiary structures through intra- and intermolecular base-pairing. They also interact with proteins to form ribonucleoproteins (RNPs), the functional units of RNA in cells. Recent methodological developments utilising high-throughput sequencing have enabled the detailed mapping of cellular RNA-protein interactions and RNA structures. While methods for the direct...
2025
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Epigenomics and transcriptomics profiles of developing zebrafish heart cells
cis-Regulatory elements (cREs) are essential for the spatio-temporal control of gene expression during development and disease. However, cRE activity is highly dependent on cell and tissue type. The developing heart is composed of several cell-types, predominantly cardiomyocytes. Therefore, cardiomyocyte-specific modelling is required to understand the cis-regulation of the developing heart. Zebrafish are an ideal model to study heart development, as they share several physiological features... -
Interplay between RNA-protein interactions and RNA structures in gene regulation
Cellular RNAs are not linear single-stranded stretches of nucleic acids as depicted in textbook cartoons but fold into secondary and tertiary structures through intra- and intermolecular base-pairing. They also interact with proteins to form ribonucleoproteins (RNPs), the functional units of RNA in cells. Recent methodological developments utilising high-throughput sequencing have enabled the detailed mapping of cellular RNA-protein interactions and RNA structures. While methods for the direct...
2024
2023
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SRSF3 shapes the structure of miR-17-92 cluster RNA and promotes selective processing of miR-17 and miR-20a
MicroRNA (miRNA) biogenesis is tightly regulated to maintain distinct miRNA expression patterns. Almost half of mammalian miRNAs are generated from miRNA clusters, but this process is not well understood. We show here that Serine-arginine rich splicing factor 3 (SRSF3) controls the processing of miR-17-92 cluster miRNAs in pluripotent and cancer cells. SRSF3 binding to multiple CNNC motifs downstream of Drosha cleavage sites within miR-17-92 is required for the efficient processing of the... -
High ploidy large cytoplasmic megakaryocytes are hematopoietic stem cells regulators and essential for platelet production
Megakaryocytes (MK) generate platelets. Recently, we and others, have reported MK also regulate hematopoietic stem cells (HSC). Here we show high ploidy large cytoplasmic megakaryocytes (LCM) are critical negative regulators of HSC and critical for platelet formation. Using a mouse knockout model (Pf4-Srsf3^(Δ/Δ)) with normal MK numbers, but essentially devoid of LCM, we demonstrate a pronounced increase in BM HSC concurrent with endogenous mobilization and extramedullary hematopoiesis. Severe...
2022
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The RNA-binding protein SRSF3 has an essential role in megakaryocyte maturation and platelet production
RNA processing is increasingly recognized as a critical control point in the regulation of different hematopoietic lineages including megakaryocytes responsible for the production of platelets. Platelets are anucleate cytoplasts that contain a rich repertoire of RNAs encoding proteins with essential platelet functions derived from the parent megakaryocyte. It is largely unknown how RNA binding proteins contribute to the development and functions of megakaryocytes and platelets. We show that...
2021
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RNA-induced inflammation and migration of precursor neurons initiates neuronal circuit regeneration in zebrafish
Tissue regeneration and functional restoration after injury are considered as stem- and progenitor-cell-driven processes. In the central nervous system, stem cell-driven repair is slow and problematic because function needs to be restored rapidly for vital tasks. In highly regenerative vertebrates, such as zebrafish, functional recovery is rapid, suggesting a capability for fast cell production and functional integration. Surprisingly, we found that migration of dormant "precursor neurons" to... -
An Engineered <em>sgsh</em> Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA
Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS...