Biology subjects

Aydin, E.

Publications and source records attributed to Aydin, E..

6 recordsLinked to original sources

bioRxiv2024

DEAD-box ATPase Dbp2 mediates mRNA release after 3'-end formation

mRNA biogenesis in the eukaryotic nucleus is a highly complex process. The numerous RNA processing steps are tightly coordinated to ensure that only fully processed transcripts are released from chromatin for export from the nucleus. Here, we present the hypothesis that fission yeast Dbp2, a ribonucleoprotein complex (RNP) remodelling ATPase of the DEAD-box family, is the key enzyme in an RNP assembly checkpoint at the 3-end of genes. We show that Dbp2 interacts with the cleavage and polyadenylation complex (CPAC) and localizes to cleavage bodies, which are enriched for 3-end processing factors and proteins involved in nuclear RNA surveillance. Upon loss of Dbp2, 3-processed, polyadenylated RNAs accumulate on chromatin and in cleavage bodies, and CPAC components are depleted from the soluble pool. Under these conditions, cells display an increased likelihood to skip polyadenylation sites and a delayed transcription termination, suggesting that levels of free CPAC components are insufficient to maintain normal levels of 3-end processing. Our data support a model in which Dbp2 is the active component of an mRNP remodelling checkpoint that licenses RNA export and is coupled to CPAC release.

molecular biology↗

bioRxiv2023

DSIF factor Spt5 coordinates transcription, maturation and exoribonucleolysis of RNA polymerase II transcripts.

The timely termination of RNA polymerase II (Pol II) transcription is critical for polymerase recycling and preventing interference with the expression of the neighbouring genes. Termination of Pol II transcription involves exoribonucleolytic decay of the nascent RNA by 5-3 exonuclease Xrn2. Xrn2 attacks the 5-PO4-end and executes degradation of the nascent RNA generated by the endonucleolytic cleavage at the poly(A) site which eventually leads to Pol II release from DNA. However, the molecular details of when and how during this process Xrn2 interacts with the Pol II elongation complex to mediate its dissociation from DNA is not understood. Here, we demonstrate that Xrn2 interacts with Pol II and Spt5, a conserved transcription factor that controls Pol II processivity and pausing. Importantly, Xrn2 activity is stimulated by Spt5 in vitro and Spt5-depleted cells show defective transcription termination. Our results support a model where Xrn2 first forms a stable complex with the elongating Pol II to acquire its full activity in degrading nascent RNA. Spt5 also promotes premature termination attenuating the expression of non-coding transcripts. By contrast, Spt5 depletion leads to Pol II retention at promoters of protein-coding genes. Pol IIs that transcribe into a gene body in the absence of Spt5 exhibit severely reduced elongation rates and defective pre-mRNA processing. We propose that Spt5 plays a major role in the production of functional mRNA by directly stimulating the activity of the RNA enzymes and preventing entry of Pol II complexes not configured to support transcription and pre-mRNA processing into elongation.

molecular biology↗

bioRxiv2022

The rhizodynamics robot: Automated imaging system for studying long-term dynamic root growth

The study of plant root growth in real time has been difficult to achieve in an automated, high-throughput, and systematic fashion. Dynamic imaging of plant roots is important in order to discover novel root growth behaviors and to deepen our understanding of how roots interact with their environments. We designed and implemented the Generating Rhizodynamic Observations Over Time (GROOT) robot, an automated, high-throughput imaging system that enables time-lapse imaging of 90 containers of plants and their roots growing in a clear gel medium over the duration of weeks to months. The system uses low-cost, widely available materials. As a proof of concept, we employed GROOT to collect images of orchid root growth of multiple species over six months. Beyond imaging plant roots, our system is highly customizable and can be used to collect time-lapse image data of different container sizes and configurations regardless of what is being imaged, making it applicable to many fields that require longitudinal time-lapse recording.

plant biology↗

bioRxiv2021

Loss of the glial glutamate transporter eaat2a leads to a combined developmental and epileptic encephalopathy in zebrafish

Astroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Hence, an impairment in EAAT2 function could lead to an imbalanced neural network excitability. Here, we investigated the functional alterations of neuronal and astroglial networks associated with the loss of function in the astroglia predominant eaat2a gene in zebrafish. We observed that eaat2a-/- mutant zebrafish larvae display recurrent spontaneous and light-induced seizures in neurons and astroglia, which coincide with an abrupt increase in extracellular glutamate levels. In stark contrast to this hyperexcitability, basal neuronal and astroglial activity was surprisingly reduced in eaat2a-/- mutant animals, which manifested in decreased overall locomotion. Our results reveal an essential and mechanistic contribution of EAAT2a in balancing brain excitability, and its direct link to epileptic seizures.

neuroscience↗

bioRxiv2021

A minimal robophysical model of quadriflagellate self-propulsion

Locomotion at the microscale is remarkably sophisticated. Microorganisms have evolved diverse strategies to move within highly viscous environments, using deformable, propulsion-generating appendages such as cilia and flagella to drive helical or undulatory motion. In single-celled algae, these appendages can be arranged in different ways around an approximately 10 {micro}m cell body, and coordinated in distinct temporal patterns. Inspired by the observation that some quadriflagellates (bearing four flagella) have an outwardly similar morphology and flagellar beat pattern, yet swim at different speeds, this study seeks to determine whether variations in swimming performance could arise solely from differences in swimming gait. Robotics approaches are particularly suited to such investigations, where the phase relationships between appendages can be readily manipulated. Here, we developed autonomous, algae-inspired robophysical models that can self-propel in a viscous fluid. These macroscopic robots (length and width = 8.5 cm, height = 2 cm) have four independently actuated flagella that oscillate back and forth under low-Reynolds number conditions (Re[~] [O] (10-1)). We tested the swimming performance of these robot models with appendages arranged in one of two distinct configurations, and coordinated in one of three distinct gaits. The gaits, namely the pronk, the trot, and the gallop, correspond to gaits adopted by distinct microalgal species. When the appendages are inserted perpendicularly around a central body, the robot achieved a net performance of 0.15 - 0.63 body lengths per cycle, with the trot gait being the fastest. Robotic swimming performance was found to be comparable to that of the algal microswimmers across all gaits. By creating a minimal robot that can successfully reproduce cilia-inspired drag-based swimming, our work paves the way for the design of next-generation devices that have the capacity to autonomously navigate aqueous environments.

biophysics↗

bioRxiv2020

Digit ratio (2D:4D) and congenital adrenal hyperplasia (CAH): Systematic literature review and meta-analysis

The ratio of length between the second and fourth fingers (2D:4D) is commonly used as an indicator of prenatal sex hormone exposure. Several approaches have been used to try to validate the measure, including examining 2D:4D in people with congenital adrenal hyperplasia (CAH), a suite of conditions characterised by elevated adrenal androgen production secondary to defective steroidogenesis. We present here a systematic review that examines the relationship between these two variables. Twelve articles relating to nine CAH cohorts were identified, and 2D:4D comparisons have been made between cases and controls in eight of these cohorts. Altogether, at least one 2D:4D variable has been compared between n=251 females with CAH and n=358 unaffected females, and between n=108 males with CAH and n=204 unaffected males. A previous meta-analysis (Honekopp & Watson, 2010) reported lower right hand (R2D:4D) and left hand (L2D:4D) digit ratios in patients with CAH relative to sex-matched controls. Our meta-analysis showed the same direction of results; however, the effects were only statistically significant for R2D:4D in males and L2D:4D in females (R2D:4D: females, p = 0.072, g = 0.591; males, p = 0.019, g = 0.513; L2D:4D: females, p = 0.020, g = 0.245; males, p = 0.334, g = 0.218), and the average effect size had reduced by 46.70%. We also found no evidence to suggest the right-left difference in 2D:4D (D[R-L]) is associated with prenatal sex hormone exposure.

developmental biology↗