Biology subjects

Mandel-Gutfreund, Y.

Publications and source records attributed to Mandel-Gutfreund, Y..

6 recordsLinked to original sources

bioRxiv2026

RBM25 exhibits distinct RNA- and chromatin-associated target programs in human embryonic stem cells

RNA-binding proteins (RBPs) are increasingly recognized to perform chromatin-associated functions in addition to their canonical roles in RNA regulation, yet how these activities are coordinated in human embryonic stem cells (hESCs) remain poorly understood. Here, we characterize distinct RNA- and chromatin-associated activities for RBM25 in hESCs. Transcriptome-wide profiling showed that RBM25 preferentially associates with transcripts involved in RNA processing and splicing, consistent with its canonical role as an RBP involved in post-transcriptional regulation. Genome-wide chromatin profiling further uncovered a distinct chromatin-associated program, with RBM25 occupying accessible promoters of actively expressed cell-cycle genes and introns predominantly associated with transcriptionally inactive neuronal genes. Interestingly, RBM25 chromatin-binding sites showed substantial co-occupancy with regions bound by the transcription factor CEBPZ in hESCs. We further show that RBM25 and CEBPZ physically interact and exhibit shared chromatin-binding patterns at both promoter and intronic regions. Importantly, reciprocal depletion experiments revealed that RBM25 is required for CEBPZ occupancy at CCAAT-containing promoters of highly expressed cell-cycle genes, whereas CEBPZ is not similarly required for RBM25 chromatin occupancy. Together, our findings establish RBM25 as a multifunctional factor with distinct roles in RNA processing and chromatin-associated regulation and reveal a context-dependent RBP-TF interaction that contributes to transcriptional regulation in hESCs.

molecular biology↗

bioRxiv2023

The Unexpected Match: STAT3-NORAD Interaction, a Novel Link in Antiviral Defense

In the intricate biological landscape, evolution often repurposes familiar elements for novel roles. This study reveals an interaction between the long non-coding RNA NORAD, noted for its role in DNA stability, and the immune-related transcription factor STAT3. Our findings indicate that NORADs binding to STAT3 facilitates its nuclear entry, suppressing the antiviral response. In the absence of NORAD, STAT3 remains cytoplasmic, enabling STAT1 to activate this response. Evidence from viral infections and clinical samples reinforces this unique role for NORAD. Intriguingly, while other functions of NORAD are conserved in evolution, this newly discovered role is unique to humans, owing to the introduction of an ALU element in hominoids. This discovery sheds new light on the evolution of antiviral defenses.

molecular biology↗

bioRxiv2023

Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors

Proteasome activity is crucial for cellular integrity, but how tissues adjust proteasome content in response to catabolic stimuli is uncertain. Here, we demonstrate that transcriptional coordination by multiple transcription factors is required to increase proteasome content and activate proteolysis in catabolic states. Using denervated mouse muscle as a model system for accelerated proteolysis in vivo, we reveal that a two-phase transcriptional program activates genes encoding proteasome subunits and assembly chaperones to boost an increase in proteasome content. Initially, gene induction is necessary to maintain basal proteasome levels, and in a more delayed phase (7-10 d after denervation) it stimulates proteasome assembly to meet cellular demand for excessive proteolysis. Intriguingly, the transcription factors PAX4 and -PALNRF-1 control the expression of proteasome among other genes in a combinatorial manner, driving cellular adaptation to muscle denervation. Consequently, PAX4 and -PALNRF-1 represent new therapeutic targets to inhibit proteolysis in catabolic diseases (e.g. type-2 diabetes, cancer).

cell biology↗

bioRxiv2022

SPIRAL: Significant Process InfeRence ALgorithm for single cell RNA-sequencing and spatial transcriptomics

1Gene expression data is complex and may hold information regarding multiple biological processes at once. We present SPIRAL, an algorithm that uses a Gaussian statistical model to produce a comprehensive overview of a plurality of significant processes detected in single cell RNA-seq or spatial transcriptomics data. SPIRAL identifies biological processes by finding sub-matrices that consist of the subset of genes involved and the subset of cells or spots. We describe the algorithmic method, the analysis pipeline and several example results. SPIRAL is available at https://spiral.technion.ac.il/.

bioinformatics↗

bioRxiv2022

LIS1 RNA-binding orchestrates the mechanosensitive properties of embryonic stem cells in AGO2-dependent and independent ways

Lissencephaly-1 (LIS1) is associated with neurodevelopmental diseases and is known to regulate the activity of the molecular motor cytoplasmic dynein. Here we show that LIS1 is essential for the viability of mouse embryonic stem cells (mESCs), and it regulates the physical properties of these cells. LIS1 dosage substantially affects gene expression, and we uncovered an unexpected interaction of LIS1 with RNA and RNA-binding proteins, most prominently the Argonaute complex. We demonstrate that LIS1 overexpression partially rescued the expression of extracellular matrix (ECM) and mechanosensitive genes conferring stiffness to Argonaute null mESCs. Collectively, our data transforms the current perspective on the roles of LIS1 in post- transcriptional regulation underlying development and mechanosensitive processes.

cell biology↗

bioRxiv2018

Adaptation to sub-optimal hosts is a driver of viral diversification in the ocean

Marine cyanophages are viruses that infect oceanic cyanobacteria, thus affecting global ecological processes. Cyanophages of the Myoviridae family are of great interest since they include generalist viruses capable of infection of a wide range of hosts including those from different cyanobacterial genera. While the influence of phages on host evolution has been studied previously, it is not known how the infection of distinct hosts influences the evolution of cyanophage populations. In marine systems this question is of special interest as the abundance of different Synechococcus and Prochlorococcus hosts constantly changes, temporally and spatially. Here, using an experimental evolution approach, we investigated the adaptation of multiple cyanophage populations to three distinct cyanobacterial hosts. We show that when infecting an \"optimal\" host, whose infection is the most efficient, phage populations accumulated only a few mutations. However, when infecting \"sub-optimal\" hosts, different, largely host-specific sets of mutations, spread in the phage populations, leading to rapid diversification into distinct subpopulations. The mutations included insertions, deletions, SNPs and codon adaptations. Most of the mutations were found in genes encoding for proteins responsible for host recognition, attachment and infection, regardless of their evolutionary conservation. Based on our results, we propose a model demonstrating how shifts in bacterial abundance, which lead to infection of \"sub-optimal\" hosts, act as a driver for rapid diversification of phage populations.

evolutionary biology↗