Biology subjects

Cisse, I. I.

Publications and source records attributed to Cisse, I. I..

4 recordsLinked to original sources

bioRxiv2025

RNA Dynamics Regulate Transcriptional Condensate Vivacity to Drive Gene Coordination

Transcriptional condensates (TCs), enriched with Mediator, orchestrate super-enhancer (SE)-driven gene expression critical for cell identity. However, how their dynamic physical properties shape transcriptional activities remains unclear. Here, we reveal a previously unknown regulatory axis wherein dynamic features of enhancer RNA (eRNA), transcribed but rapidly degraded by the RNA exosome, maintain optimal TC fluidity and stability. Depletion of RNA exosome disrupts TC integrity, altering Mediator and Pol II colocalization, in embryonic stem cells. This TC perturbation attenuates proper transcriptional regulator loading and pause-release regulation, enhances transcriptional noise, and diminishes coordinated eRNA-mRNA expression for SE-associated genes. Multi-omics analyses, live-cell imaging, and computational modeling collectively demonstrate that RNA turnover modulates TC vivacity, facilitating widespread chromatin contacts between SE-containing active A compartments and coordinated transcriptional bursts across SE-associated genes. Our findings establish RNA-dependent condensate dynamics as an essential quality-control mechanism that fine-tunes global transcriptional coordination, maintaining cellular homeostasis and cell identity. HighlightsO_LIRNA exosome is required for the homeostasis of transcriptional condensates (TCs) C_LIO_LIRNA synthesis and decay optimize the fluidity and dynamic properties of TCs C_LIO_LITCs maintain the transcriptional consistency of super-enhancer (SE) genes C_LIO_LITCs support contacts of SE-containing A compartments for coordinated transcription C_LI

molecular biology↗

bioRxiv2017

A First Order Phase Transition Underlies the Formation of Sub-Diffractive Protein Aggregates in Mammalian Cells

Failure in protein quality control can often lead to protein aggregation, yet in neuro-degenerative diseases, by the time aggregates can be seen, the cells have advanced well into the disease pathology. Here, we develop a quantitative imaging approach to study the protein aggregation process in living mammalian cells with unprecedented spatio-temporal resolution. We find that sub-diffractive precursor aggregates may form even in untreated cells, and their size distribution is exactly as predicted for a system undergoing a first order phase transition. Practically, this implies that as soon as aggregates reach a critical size (Rc = 162 {+/-} 4 nm untreated cells), they will spontaneously grow into large inclusions. Our data suggest that a previously uncharacterized, RuvBL1 dependent mechanism clears aggregates above the critical size. Our study unveils the existence of sub-diffractive aggregates in living cells; and the strong agreement between cellular data and a nucleation theory, based on first order phase transition, provides insight into regulatory steps in the early stages of aggregate formation in vivo.

biophysics↗

bioRxiv2017

qSR: A software for quantitative analysis of single molecule and super-resolution data

Single-molecule based super-resolution microscopy (Betzig et al., 2006; Hess et al., 2006; Rust et al., 2006) provides insight into the spatiotemporal organization and dynamics of biomolecules at the length scale of ten to hundreds of nanometers, which is most relevant to protein clustering in a broad range of cellular processes. A series of quantitative analysis approaches have been developed to infer the characteristic size of protein clustering via pair correlation analysis (Sengupta et al., 2013; Sengupta et al., 2011; Veatch et al., 2012) or to merge multiple blinking localizations from single fluorophores (Annibale et al., 2011), to identify clusters based on density of detections (Ester, 1996), and to measure temporal dynamics of protein clustering in living cells (Cho et al., 2016a; ...

biophysics↗

bioRxiv2017

Cell-cycle dependent organization and dynamics of RNA Polymerase I in live human cells

RNA Polymerase I (Pol I) is responsible for over 60% of transcriptional output in human cells, yet basic questions concerning the spatial and temporal organization of the polymerase remain unanswered. Here we investigate how mammalian cells rely on Pol I organization throughout the cell cycle to balance different needs, from complete transcription shut down to massive increase in protein synthesis (and thus ribosomal RNA synthesis) before cell division. In contrast to our previous reports on RNA Polymerase II, Pol I clusters are stable with active transcription, and the presence of transient Pol I clusters correlates with inactive ribosomal transcription. Our results suggest that both stable and transient populations Pol I clusters co-exist in individual living cells, and their relative fraction may directly reflect the global gene expression need of the cell.

biophysics↗