Biology subjects

Herrero-Ruiz, A.

Publications and source records attributed to Herrero-Ruiz, A..

3 recordsLinked to original sources

bioRxiv2025

Hybrid bioinks for embedded bioprinting of an artery model

The integration of biomaterials with living cells and stimuli-responsive materials can be employed to create bioinks capable of generating 3D in vitro models that better recapitulate native tissues. We introduce a multilayered artery model that combines hybrid multifunctional materials including a stimuli-responsive polymeric ink to mimic the tunica adventitia arterial wall, and an extracellular matrix (ECM)-based bioink for the tunica media artery layer. The stimuli-responsive hybrid layer integrates inorganic (plasmonic nanoparticles) and organic (polymers) components, providing structural support and introducing diverse functionalities to the system. The cell-laden bioink consists of human vascular smooth muscle cells (vSMC) within a hydrogel based on porcine artery-derived decellularized extracellular matrix (dECM) that fosters optimal cell growth and proliferation. An embedding bioprinting technique was employed for the fabrication of the multimaterial artery model consisting of concentric cylinders. The dimensions of the 3D model and the bioprinting parameters were fine-tuned to ensure effective crosslinking of the multiple concentric layers resulting in the creation of self-supporting constructs. We demonstrate the effectiveness of the hybrid bioink composition and bioprinting parameters in supporting cell viability and proliferation within the multilayered construct, expanding the possibilities of employing novel multi-component materials for the fabrication of 3D vasculature models resembling the structure of native blood vessels.

bioengineering↗

bioRxiv2023

HSP70 binds to specific non-coding RNA and regulates human RNA Polymerase III

Molecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone Heat-Shock Protein 70 (HSP70) binds to non-coding RNA transcribed by RNA Polymerase III (Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by Pol III. Detailed biochemical analyses showed that HSP70 facilitates transcription of its target non-coding RNA by binding to Pol III. Thus our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in neurodegeneration and cancer.

biochemistry↗

bioRxiv2020

Control of RNA polymerase II promoter-proximal pausing by DNA supercoiling

The accumulation of topological stress in the form of DNA supercoiling is inherent to the advance of RNA polymerase II (Pol II) complexes, and needs to be resolved by DNA topoisomerases to sustain productive transcriptional elongation. Topoisomerases are therefore considered general positive facilitators of transcription. Here we show that, in contrast to this general assumption, human topoisomerase IIa accumulates at gene promoters, where it removes transcription-associated negative DNA supercoiling and represses transcription by enforcing promoter-proximal pausing of Pol II. We demonstrate that this topological balance is essential to maintain Immediate Early Genes under basal repression conditions, and that its disruption creates a positive feedback loop that explains their typical bursting behavior in response to stimulus. We therefore describe the control of promoter DNA supercoiling by topoisomerases as a novel layer for the regulation of gene expression, which can act as a molecular switch to rapidly activate transcription.

molecular biology↗