Biology subjects

Ponti, R. D.

Publications and source records attributed to Ponti, R. D..

3 recordsLinked to original sources

bioRxiv2026

Phase Separation Potential of Marsupial RSX RNA Reveals Convergent Evolution of X-Chromosome Inactivation Mechanisms

Background: X-chromosome inactivation (XCI) evolved independently in eutherian and marsupial mammals, where it is orchestrated by the unrelated long non-coding RNAs Xist and RSX, respectively. Xist organizes a repressive nuclear compartment through multivalent RNA-protein interactions, but whether RSX exploits similar biophysical principles remains unknown. A recent paper has identified bona fide RSX interacting proteins. Results: We integrated proteome-scale RNA-protein interaction prediction, experimental validation, phase-separation propensity analysis, functional annotation and comparative RNA-structure modelling to characterize the RSX interaction landscape. Using catRAPID, we ranked 1,168 RNA-binding proteins from the native Monodelphis domestica proteome. Predictions were significantly enriched for experimentally identified RSX interactors, with 4.85-fold enrichment among the top 50 candidates (P approximately 1.6 x 10-5), increasing to approximately eightfold for proteins shared by the experimental RSX and Xist interactomes (P approximately 2 x 10-6). Among 30 high-confidence RSX interactors, 13 were experimentally supported, 17 were previously unrecognized candidates and 17 exhibited high phase-separation propensity. The network was enriched in ribonucleoprotein granules and nuclear bodies and converged on m6A regulators and SR-family splicing factors. Comparative modelling detected no conserved secondary or tertiary architecture between RSX and Xist. Conclusions: RSX and Xist appear to have converged not through RNA sequence or global structure, but through recruitment of related, condensation-prone protein networks. These findings identify interaction-network and biophysical convergence as a potential principle of lncRNA-mediated chromosome regulation and provide testable candidates for determining whether RSX establishes a condensate-like compartment on the marsupial inactive X.

bioinformatics↗

bioRxiv2024

Subgenomic flaviviral RNAs and human proteins: in silico exploration of anti-host defense mechanisms

BackgroundFlaviviruses pose significant global health threats, infecting over 300 million people annually. Among their evasion strategies, the production of subgenomic flaviviral RNAs (sfRNAs) from the 3 UTR of viral genomes is particularly notable. These sfRNAs interact with human proteins, disrupting key cellular processes such as RNA splicing and the interferon response. ResultsUtilizing a comprehensive in silico approach with the catRAPID algorithm, we analyzed over 300,000 interactions between sfRNAs and human proteins derived from more than 8,000 flavivirus genomes, including Dengue, Zika, Yellow Fever, West Nile, and Japanese Encephalitis viruses. Our study not only validated known interactions but also revealed novel human proteins that could be involved in sfRNA-mediated host defense evasion, including helicases, splicing factors, and chemokines. We propose that sfRNAs function as molecular sponges, sequestering specific proteins indicative of sfRNA-forming regions across flaviviruses. These findings represent a valuable resource for diagnostic and therapeutic developments. ConclusionsOur findings significantly expand the known interactome of sfRNAs with human proteins, underscoring their role in modulating host cellular pathways. By providing the first extensive atlas of sfRNA interactions, we offer new insights into how flaviviruses can manipulate host cellular machinery to facilitate viral survival and persistence. Intriguingly, we predict interaction with stress granules, a critical component of the cellular response to viral infection, suggesting a mechanism by which flaviviruses inhibit their formation to evade host defenses. This atlas not only serves as a resource for exploring therapeutic targets but also aids in the identification of sfRNA biomarkers for improved flavivirus diagnostics.

biochemistry↗

bioRxiv2022

A high-throughput approach to predict A-to-I effects on RNA structure indicates a change of double-stranded content in non-coding RNAs

RNA molecules undergo a number of chemical modifications whose effects can alter their structure and molecular interactions. Previous studies have shown that RNA editing can impact the formation of ribonucleoprotein complexes and influence the assembly of membrane-less organelles such as stress-granules. For instance, N6-methyladenosine (m6A) enhances SG formation and N1-methyladenosine (m1A) prevents their transition to solid-like aggregates. Yet, very little is known about adenosine to inosine (A-to-I) modification that is very abundant in human cells and not only impacts mRNAs but also non-coding RNAs. Here, we built the CROSSalive predictor of A-to-I effects on RNA structure based on high-throughput in-cell experiments. Our method shows an accuracy of 90% in predicting the single and double-stranded content of transcripts and identifies a general enrichment of double-stranded regions caused by A-to-I in long intergenic non-coding RNAs (lincRNAs). For the individual cases of NEAT1, NORAD and XIST, we investigated the relationship between A-to-I editing and interactions with RNA-binding proteins using available CLIP data. We found that A-to-I editing is linked to alteration of interaction sites with proteins involved in phase-separation, which suggests that RNP assembly can be influenced by A-to-I. CROSSalive is available at http://service.tartaglialab.com/new_submission/crossalive.

biochemistry↗