Biology subjects

Hashimshony, T.

Publications and source records attributed to Hashimshony, T..

5 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

Gene regulatory patterning codes in early cell fate specification of the C. elegans embryo

Pattern formation originates during embryogenesis by a series of symmetry-breaking steps throughout an expanding cell lineage. In Drosophila, classic work has shown that the embryo segmentation is established by morphogens within a syncytium, and the subsequent action of the gap, pair-rule, and segment polarity genes. This classic model however does not translate directly to species that lack a syncytium - such as C. elegans - where cell fate is specified by cell-autonomous cell lineage programs and their inter-signaling. Previous single-cell RNA-Seq studies in C. elegans have analyzed cells from a mixed suspension of cells from many embryos to study late differentiation stages, or individual early stage embryos to study early gene expression in the embryo. To study the intermediate stages of early and late gastrulation (28- to 102- cells stages) missed by these approaches, here we determine the transcriptomes of the 1- to 102-cell stage to identify 119 embryonic cell-states during cell-fate specification, including equivalence-group cell identities. We find that gene expression programs are modular according to the sub-cell lineages, each establishing a set of stripes by combinations of transcription factor gene expression across the anterior-posterior axis. In particular, expression of the homeodomain genes establishes a comprehensive lineage-specific positioning system throughout the embryo beginning at the 28-cell stage. Moreover, we find that genes that segment the entire embryo in Drosophila have orthologs in C. elegans that exhibit sub-lineage specific expression. These results suggest that the C. elegans embryo is patterned by a juxtaposition of distinct lineage-specific gene regulatory programs each with a unique encoding of cell location and fate. This use of homologous gene regulatory patterning codes suggests a deep homology of cell fate specification programs across diverse modes of development.

developmental 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↗

bioRxiv2019

Developmental dynamics are a proxy for selective pressures on alternatively polyadenylated isoforms

Alternative polyadenylation (APA) leads to multiple transcripts from the same gene, yet their distinct functional attributes remain largely unknown. Here, we introduce APA-seq to detect the expression levels of APA isoforms from 3-end RNA-Seq data by exploiting both paired-end reads for gene isoform identification and quantification. Applying APA-seq, we detected the expression levels of APA isoforms from RNA-Seq data of single C. elegans embryos, and studied the patterns of 3 UTR isoform expression throughout embryogenesis. We found that global changes in APA usage demarcate developmental stages, suggesting a requirement for distinct 3 UTR isoforms throughout embryogenesis. We distinguished two classes of genes, depending upon the correlation between the temporal profiles of their isoforms: those with highly correlated isoforms (HCI) and those with lowly correlated isoforms (LCI) across time. This led us to hypothesize that variants produced with similar expression profiles may be the product of biological noise, while the LCI variants may be under tighter selection and consequently their distinct 3 UTR isoforms are more likely to have functional consequences. Supporting this notion, we found that LCI genes have significantly more miRNA binding sites, more correlated expression profiles with those of their targeting miRNAs and a relative lack of correspondence between their transcription and protein abundances. Collectively, our results suggest that a lack of coherence among the regulation of 3 UTR isoforms is a proxy for selective pressures acting upon APA usage and consequently for their functional relevance.

molecular biology↗