A lab of biochemists, cell biologists and microscopists asking how the cell organizes RNA in space and time — from single transcripts on their way to nuclear pores to ribosomes within the multi-layered nucleolus.
The lab combines single-molecule and super-resolution microscopy with genetics and biochemistry to work out the rules that govern RNA metabolism — how messenger RNAs are packaged, sorted, exported, and translated, and how long non-coding RNAs find their place inside the nucleus.
We are interested in the everyday choreography of the cell: which RNAs leave through the nuclear pore, which ones stay, and how their organization sets up the next step of gene expression. Defects in these steps are at the heart of cancer and neurodegenerative diseases like ALS, so the basic biology has a long arm.
From the geometry of a single mRNP to the architecture of the nuclear pore, our work spans scales without leaving the cell.
RNPs are central to cellular function, and disruption of their components contributes to diseases ranging from cancer to neurodegeneration. Using single-molecule and super-resolution microscopy alongside genomics and proteomics, we ask how RNPs are organized inside cells and how this organization breaks down in disease.
The nuclear pore complex (NPC) is the sole gateway between the nucleus and the cytoplasm. We investigate how NPCs select which RNAs to export and which to retain, and whether individual pores carry out distinct functions.
The nucleus is highly organized in space, and its subcompartments play key roles in carrying out gene expression programs. We explore how membraneless bodies like the nucleolus and nuclear speckles contribute to the regulation of gene expression.
How the NPC sorts which RNAs to export and which to keep behind — with a soft spot for its most enigmatic part, the nuclear basket.
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RNA is not a string but a 3D RNA–protein assembly. We read its shape — and how that shape tunes splicing, translation and disease.
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Following ribosome assembly inside the nucleolus's phase-separated layers, one transcript at a time, in search of specialized ribosomes.
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The only autonomously mobile element in our genome — silenced in healthy tissue, derepressed in cancer. We watch its life cycle live.
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Introns are usually called debris. We follow what happens after the cut — and why faulty intron turnover makes cells vulnerable to disease.
Open page →A small, mixed group of biochemists, cell biologists and quantitative microscopists.
A small selection — see Google Scholar and the Publications page for the complete list.
The lab welcomes applications for PhD and postdoctoral candidates interested in RNA biology, nuclear organization, single-molecule and super-resolution imaging and/or RNP biochemistry.
Please write directly with a CV and a short cover letter describing your scientific interests.
Email DanielFind us in Montréal.
AddressPavillon J.-Armand-Bombardier ↗
Université de Montréal · Polytechnique Montréal
Montréal, Québec, Canada
DepartmentBiochemistry & Molecular Medicine
Université de Montréal
We study how the nuclear pore complex (NPC) modulates the export of mRNAs while retaining others, like lncRNAs and unprocessed mRNAs. The selection rules remain unclear, and many proteins involved are mutated in diseases such as ALS.
We have a particular interest in one of the most mysterious parts of the NPC: the nuclear basket.
In cells, RNA is not just a long string of nucleotides but an RNA–protein (RNP) assembly, in which different regions of these complexes communicate with their environment to regulate gene expression. While the RNP proteome is well characterized, little is known about how mRNPs are organized as 3D assemblies.
This 3D organization is critical for many aspects of RNA metabolism — for example, mRNA organization for efficient translation, or intron organization for accurate splicing. We use microscopy, biochemical, and structural approaches to study RNP organization in healthy cells and in the context of disease-associated mutations in specific RNA-binding proteins.
Ribosomes are complex RNA–protein machines essential for protein synthesis, and defects in their assembly cause a range of diseases. They are built in the nucleolus, where a large rRNA precursor is transcribed and processed into multiple rRNAs that assemble with proteins into the ribosomal subunits.
This occurs within the nucleolus's multilayered, phase-separated compartments. We use single-molecule imaging to investigate the spatio-temporal progression of ribosome biogenesis, aiming to understand how this complex process is executed and whether it gives rise to specialized ribosomes.
Long Interspersed Nuclear Element-1 (LINE-1) is the only autonomously mobile genetic element in the human genome, accounting for roughly 17 percent of human DNA. Normally silenced in adult somatic tissues via DNA methylation, its derepression is a near-universal hallmark of many human cancers, particularly carcinomas.
Despite extensive characterization of LINE-1 expression in cancer, key aspects of its endogenous life cycle remain poorly understood, including the role of cytoplasmic ORF1p granules used as biomarkers. We use single-molecule and super-resolution microscopy, proteomic and genomic approaches to dissect the spatiotemporal regulation of LINE-1.
Introns are typically viewed as splicing byproducts, rapidly degraded following excision from pre-mRNAs. Yet when their turnover is disrupted by mutation, disease phenotypes emerge — including increased susceptibility to viral infections.
We investigate post-intron metabolism through genomic, proteomic, and microscopy approaches to understand how defective intron turnover drives disease.
A chronological selection of work from the lab and collaborations. The complete, always-current list lives on PubMed and Google Scholar:
Daniel Zenklusen has co-authored 51+ peer-reviewed papers across more than two decades of RNA biology. For the complete, continuously updated list — including older work and book chapters — please visit PubMed or Google Scholar.
mRNAs are essential intermediates in gene expression, bridging the genetic information encoded in DNA and the proteins that execute cellular function. Before translation can occur, these transcripts must traverse the nuclear pore complex (NPC) — the sole gateway between nucleus and cytoplasm — a process whose underlying mechanisms remain incompletely understood.
My project centers on TPR, a key structural component of the nuclear basket, a filamentous scaffold that extends from the cytoplasmic face of the NPC into the nuclear interior. As the likely first point of contact between export-competent mRNAs and the NPC, the nuclear basket is uniquely positioned to act as a gatekeeper of nuclear export.
I aim to dissect the role of TPR and the nuclear basket in guiding mRNAs toward the central channel of the NPC, determine whether this structure actively regulates pore access, and uncover the full breadth of its functions in mRNA biogenesis and export.
The nucleolus is a dynamic nuclear compartment whose organization can shift in response to cellular conditions, though the triggers of these changes are not fully understood.
During my summer project, I am using immunofluorescence and RNA FISH microscopy to visualize the nucleolus and characterize how its structure responds to different stimuli.
Cytoplasmic mRNAs cycle between translationally active and inactive states, yet the mechanisms governing these transitions remain poorly understood.
My project investigates how the composition and structure of cytoplasmic mRNP complexes regulate these transitions, combining proteomics and cryo-EM.
“If you look at nature carefully and really pay attention, then, if you’re lucky, you can catch a glimpse of something deeply hidden.” — Albert Einstein
I study how genetic information is curated, expressed, and regulated. Using cutting-edge imaging modalities, I explore how RNA-binding proteins and molecular machines shape RNA processing, how the nucleus organizes itself into compartments, and how evolutionary dialogue unfolds between retrotransposons and host cells.
My research is an attempt to look at life in super resolution to get a glimpse of the hidden logic by which molecular soup comes alive.
I focus on two main projects in my PhD. In my primary project, I am developing a live-cell single-particle tracking approach to resolve the functional RNA-bound states of intron-binding proteins, and to investigate how they shape intron topology, suppress retrotransposon-derived exonization, and retain transcripts at nuclear speckle boundaries during co- and post-transcriptional splicing.
My second project explores the cytoplasmic life of LINE-1 RNA through smFISH and super-resolution imaging, asking whether its granules serve as vehicles for retrotransposon propagation or as cellular compartments that restrain these virus-like elements.
“If I have seen further, it is by standing on the shoulders of Giants.” — Isaac Newton
Ribosome biogenesis is an intricately regulated process that takes place in the nucleolus, a layered, phase-separated organelle. Although this process has been extensively studied, its spatiotemporal organization remains an enigma.
By building upon the many outstanding ideas and findings from the “giants” in the field, we can help ourselves imagine, push the boundaries of knowledge, and possibly learn a little more together about ribosome biology.
To address these current unknowns, in my Ph.D. projects, I use live-cell single-molecule microscopy to study the dynamics of ribosomal components and assembly intermediates across nucleolar subcompartments. This new approach will bring a fresh perspective that bridges the biological and biophysical fields, enhancing our understanding of ribosome biology and beyond.
Splicing is a central step in mRNA processing, yet the biology of introns themselves remains one of its most enigmatic aspects. Introns are excised as lariats and are generally thought to be rapidly degraded after splicing — a process that depends on specialized enzymes, including the debranching enzyme DBR1, due to the unusual branched structure of lariats.
Defects in lariat processing and turnover have been linked to diseases ranging from cancer to increased sensitivity to viral infection, but a mechanistic understanding of these phenotypes is still largely missing.
My Master’s project aims to uncover what happens when lariats are not properly turned over, approached from the perspective of a single-molecule RNA imaging microscopist.
The Zenklusen lab studies how eukaryotic cells regulate the everyday choreography of gene expression: which RNAs leave the nucleus, which stay behind, and how their organization sets up the next steps of expression and decay. Most of the work happens at the level of single molecules and single cells, using yeast, mammalian and human cancer cell models.
Over more than two decades, Daniel has helped develop the imaging tools that make this kind of biology possible — quantitative smFISH and MS2/PP7 live-cell imaging during his postdoc in Robert Singer’s lab, and 3D-SIM/STORM mRNP mapping more recently in Montreal — and applied them to a series of questions about RNA: how mRNAs are packaged into mRNPs — both those on their way to the cytoplasm and intronic RNAs before and after splicing, how those particles are selected by the nuclear basket of the nuclear pore, how non-coding RNAs tune transcription, and, most recently, how cells take care of repeat elements — whether from normally dormant LINE-1 or from Alu elements often hosted within introns.
Current projects in the lab span four themes — RNA transport through the nuclear pore, (pre-)mRNP topology, ribosome biogenesis and nucleolar organization, LINE-1 biology, and post-splicing intron metabolism — held together by a shared commitment to quantitative, single-molecule readouts of cellular biology.
Selected from 50+ peer-reviewed papers across four phases of the career