Biology subjects

Abdou, A.

Publications and source records attributed to Abdou, A..

4 recordsLinked to original sources

bioRxiv2023

Large-scale map of RNA binding protein interactomes across the mRNA life-cycle

Messenger RNAs (mRNAs) interact with RNA-binding proteins (RBPs) in diverse ribonucleoprotein complexes (RNPs) during distinct life-cycle stages for their processing and maturation. While substantial attention has focused on understanding RNA regulation by assigning proteins, particularly RBPs, to specific RNA substrates, there has been considerably less exploration leveraging protein-protein interaction (PPI) methodologies to identify and study the role of proteins in mRNA life-cycle stages. To address this gap, we generated an RNA-aware RBP-centric PPI map across the mRNA life-cycle by immunopurification (IP-MS) of [~]100 endogenous RBPs across the life-cycle in the presence or absence of RNase, augmented by size exclusion chromatography (SEC-MS). Aside from confirming 8,700 known and discovering 20,359 novel interactions between 1125 proteins, we determined that 73% of our IP interactions are regulated by the presence of RNA. Our PPI data enables us to link proteins to life-cycle stage functions, highlighting that nearly half of the proteins participate in at least two distinct stages. We show that one of the most highly interconnected proteins, ERH, engages in multiple RNA processes, including via interactions with nuclear speckles and the mRNA export machinery. We also demonstrate that the spliceosomal protein SNRNP200 participates in distinct stress granule-associated RNPs and occupies different RNA target regions in the cytoplasm during stress. Our comprehensive RBP-focused PPI network is a novel resource for identifying multi-stage RBPs and exploring RBP complexes in RNA maturation. HIGHLIGHTSO_LIAn RBP-centric RNA-aware PPI network focuses on the mRNA life-cycle in human cells C_LIO_LIPrey-prey correlation analysis assigns prey proteins to life-cycle stages, of which 536 proteins (half of the network) interact with multiple steps C_LIO_LIERH is highly connected to multiple RNPs to affect nuclear speckle organization and mRNA export C_LIO_LISplicing factor SNRNP200 interacts with stress granule proteins and has distinct RNA occupancy in the cytoplasm C_LI

systems biology↗

bioRxiv2023

Cerebellar granular neuron progenitors exit their germinative niche via Barhl1 mediated silencing of T-Cell Factor transcriptional activity

SUMMARYT-Cell Factors (TCFs) are the main transcriptional effectors of Wnt/{beta}-catenin signaling. TCF responsiveness is a hallmark of self-renewal in mouse embryonic, and adult, neural stem cells (NSC). However, in vivo contribution(s) of TCF activities in long-lived NSCs are poorly understood. Granule neuron progenitors (GNP) in the upper rhombic lip (URL) are long-lived NSCs which express Atoh1 and generate cerebellar granule neurons. Using functional and transcriptomic approaches in amphibian, we demonstrate that TCFs are active in the URL, and are strictly necessary for the emergence and maintenance of the GNP germinative zone. We identify BarH-like 1 (Barhl1), a direct target of Atoh1, as a gate keeper for GNP exit from the URL, through silencing of TCF transcriptional activity. Our transcriptomic and in silico analysis identifies Barhl1/TCF URL target genes, and confirms our functional data. Our study provides in vivo evidence that inhibition of TCF repressive activity is necessary for maintenance of the URL, a long-lived neural germinative niche.

developmental biology↗

bioRxiv2019

β-adrenergic signaling modulates cancer cell mechanotype through a RhoA-ROCK-myosin II axis

The ability of cells to deform and generate forces are key mechanical properties that are implicated in metastasis. While various soluble and mechanical cues are known to regulate cancer cell mechanical phenotype or mechanotype, our knowledge of how cells translate external signals into changes in mechanotype is still emerging. We previously discovered that activation of {beta}-adrenergic signaling, which results from soluble stress hormone cues, causes cancer cells to be stiffer or less deformable; this stiffer mechanotype was associated with increased cell motility and invasion. Here, we characterize how {beta}-adrenergic activation is translated into changes in cellular mechanotype by identifying molecular mediators that regulate key components of mechanotype including cellular deformability, traction forces, and non-muscle myosin II (NMII) activity. Using a micropillar assay and computational modelling, we determine that {beta}AR activation increases cellular force generation by increasing the number of actin-myosin binding events; this mechanism is distinct from how cells increase force production in response to matrix stiffness, suggesting that cells regulate their mechanotype using a complementary mechanism in response to stress hormone cues. To identify the molecules that modulate cellular mechanotype with {beta}AR activation, we use a high throughput filtration platform to screen the effects of pharmacologic and genetic perturbations on {beta}AR regulation of whole cell deformability. Our results indicate that {beta}AR activation decreases cancer cell deformability and increases invasion by signaling through RhoA, ROCK, and NMII. Our findings establish {beta}AR-RhoA-ROCK-NMII as a primary signaling axis that mediates cancer cell mechanotype, which provides a foundation for future interventions to stop metastasis.

cancer biology↗

bioRxiv2018

The global burden of trichiasis in 2016

BackgroundTrichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation.\n\nMethodsWe obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available.\n\nFindingsInternally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non-standardized estimates for 398 districts, adjusted by x0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million).\n\nInterpretationThe 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.\n\nAuthor SummaryAs an individual with trichiasis blinks, the eyelashes abrade the cornea, which can lead to corneal opacity and blindness. Through high quality surgery, which involves correcting the position of the in-turned eyelid, it is possible to reduce the number of people with trichiasis. An accurate estimate of the number of persons with trichiasis and their geographical distribution are needed in order to effectively align resources for surgery and other necessary services. We obtained district-level trichiasis prevalence estimates for 44 endemic and previously-endemic countries. We used the most recently available data and expert assessments to estimate the global burden of trichiasis. We estimated that in 2016 the global burden was 2.8 million cases (95% CI 1.1-5.2 million).\n\nThe 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

epidemiology↗