Biology subjects

Jaberi-Lashkari, N.

Publications and source records attributed to Jaberi-Lashkari, N..

4 recordsLinked to original sources

bioRxiv2025

Deep Learning of Functional Perturbations from Condensate Morphology

Biomolecular condensates compartmentalize the interior of living cells to spatiotemporally organize complex functions, yet linking molecular interactions within condensates to their mesoscale organization remains a major challenge. To bridge this gap, we developed a neural network-based framework - Deep-Phase - that uses microscopy images to quantitatively classify condensate morphology changes resulting from pharmacological alterations in associated biochemical processes. We use Deep-Phase to precisely quantify time- and concentration-dependent structural perturbations to the multiphase nucleolus and show that they are tightly coupled to potencies of drugs inhibiting rRNA transcription and processing. Applying Deep-Phase in a chemical screen, we identify a unique nucleolar morphology and discover a role for a DNA topoisomerase in rRNA processing. Mechanistic studies of this morphology provide insights into how interfaces between nucleolar subcompartments are maintained. We demonstrate Deep-Phases adaptability to diverse cell lines, labels, and condensates, offering a powerful platform for uncovering cellular organizing principles and therapeutic targets. HighlightsO_LIA deep learning framework, Deep-Phase, classifies and quantifies drug-induced changes in morphologies of nucleoli, nucleolar speckles, and viral cytoplasmic condensates, directly from images. C_LIO_LITime- and concentration-dependent morphological responses to perturbation predict associated disruptions in RNA transcription and processing. C_LIO_LIUsing Deep-Phase in a high-content small molecule screen reveals a unique nucleolar morphology induced by TOP1 inhibition. C_LIO_LITOP1 inhibition leads to reduced levels and processing of large ribosomal subunit precursors and provides a mechanism for maintenance of nucleolar phase boundaries. C_LI

molecular biology↗

bioRxiv2022

TCOF1 is a single-component scaffold of the nucleolar fibrillar center

Many of the biological structures that exist across the tree of life are built on self-interacting scaffolds, from the actin cytoskeleton to the collagen extracellular matrix. Intracellular membraneless organelles, such as the nucleolus, are biological structures consisting of hundreds of dynamically interacting components, yet it is unclear whether the underlying organization of these complex assemblies can be scaffolded by such self-interacting components. Here, we show that TCOF1 is a single-component scaffold of the nucleolar fibrillar center (FC), based on thermodynamics of its assembly in cells, as well as sufficiency and loss-of-function experiments. TCOF1 is necessary for the formation of the FC, and defines the FC through assembly mediated by homotypic interactions of its Serine/Glutamate (S/E)-rich low-complexity regions (LCRs). Ultimately, introduction of TCOF1 into a species that lacks the FC is sufficient to form an FC-like nucleolar subcompartment. Thus, we demonstrate how a single protein component can explain the formation and evolution of a complex biological structure.

biophysics↗

bioRxiv2022

A unified view of LCRs across species

Low complexity regions (LCRs) play a role in a variety of important biological processes, yet we lack a unified view of their sequences, features, relationships, and functions. Here, we use dotplots and dimensionality reduction to systematically define LCR type/copy relationships and create a map of LCR sequence space capable of integrating LCR features and functions. By defining LCR relationships across the proteome, we provide insight into how LCR type and copy number contribute to higher order assemblies, such as the importance of K-rich LCR copy number for assembly of the nucleolar protein RPA43 in vivo and in vitro. With LCR maps, we reveal the underlying structure of LCR sequence space, and relate differential occupancy in this space to the conservation and emergence of higher order assemblies, including the metazoan extracellular matrix and plant cell wall. Together, LCR relationships and maps uncover and identify scaffold-client relationships among E-rich LCR-containing proteins in the nucleolus, and revealed previously undescribed regions of LCR sequence space with signatures of higher order assemblies, including a teleost-specific T/H-rich sequence space. Thus, this unified view of LCRs enables discovery of how LCRs encode higher order assemblies of organisms.

cell biology↗

bioRxiv2020

The RNA-binding protein, Rasputin/G3BP, enhances the stability and translation of its target mRNAs

G3BP RNA-binding proteins are important components of stress granules (SGs). Here we analyze the role of Drosophila G3BP, Rasputin (RIN), in unstressed cells, where RIN is not SG associated. Immunoprecipitation followed by microarray analysis identified over 550 mRNAs that copurify with RIN. The mRNAs found in SGs are long and translationally silent. In contrast, we find that RIN-bound mRNAs, which encode core components of the transcription, splicing and translation machinery, are short, stable and highly translated. We show that RIN is associated with polysomes and provide evidence for a direct role for RIN and its human homologs in stabilizing and upregulating the translation of their target mRNAs. We propose that when cells are stressed the resulting incorporation of RIN/G3BPs into SGs sequesters them away from their short target mRNAs. This would downregulate the expression of these transcripts, even though they are not incorporated into stress granules.

genomics↗