Biology subjects

Di Marco, S.

Publications and source records attributed to Di Marco, S..

3 recordsLinked to original sources

bioRxiv2024

All-atom simulations elucidate the molecular mechanismunderlying RNA-membrane interactions

RNA-membrane interactions are starting to emerge as an important organizing force in both natural and synthetic biological systems. Notably, RNA molecules were recently discovered to be present on the extracellular surface of living cells, where they mediate intercellular signalling. Furthermore, RNA-membrane interactions influence the efficacy of lipid-based RNA delivery systems. However, the molecular terms driving RNA localisation at the membrane remain poorly understood. In this work, we investigate how RNA-phospholipid membrane interactions occur, by means of all-atom simulations. We find that among the four RNA nucleobases guanine exhibits the strongest interaction with the membrane due to extensive hydrogen bond formation. Additionally, we show that intra-RNA base pairing present in organised RNA structures significantly hinders RNA binding to the membrane. Elucidating the molecular details of RNA-membrane association will importantly contribute to improving the design of RNA-based drugs as well as lipid-based RNA delivery systems and to parsing out RNA transport and localisation mechanisms.

biophysics↗

bioRxiv2024

A membrane-targeted photoswitch restores physiological ON/OFF responses to light in the degenerate retina

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch which modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in two distinct genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances. Intravitreally injected Ziapin2 in fully blind rd10 mice restored light-driven behavior and optomotor reflexes. The results indicate that Ziapin2 is a promising molecule for reinstating physiological visual responses in the late stages of retinal degeneration.

neuroscience↗

bioRxiv2023

pADP-ribosylation Regulates the Cytoplasmic Localization, Cleavage and Pro-apoptotic Function of HuR

HuR (ElavL1) is one of the main posttranscriptional regulators that determines cell fate. While the role of HuR in apoptosis is well-established, the posttranslational modifications that governs this function remain elusive. In this study we show that PARP1/2-mediated poly(ADP)-ribosylation (PARylation) is instrumental in the pro-apoptotic function of HuR. During apoptosis or in cells depleted of PARP1/2 enzymes, a substantial reduction in HuR PARylation is observed. This results in the cytoplasmic accumulation and the cleavage of HuR, both of which are essential events for apoptosis. These effects are mediated by a pADP-ribose (PAR) binding motif within the HuR-HNS region (HuR PAR Binding Site (HuR-PBS)). Under normal conditions, the association of HuR-PBS with PAR is responsible for the nuclear retention of HuR. Mutations within this motif prevents the binding of HuR to its import factor TRN2, leading to its cytoplasmic accumulation and cleavage. Collectively, our findings underscore the role of PARylation in controlling the proapoptotic function of HuR, offering insight into the mechanism by which PARP1/2 enzymes regulate cell fate and adaptation to various assaults.

cell biology↗