Biology subjects

Tartaglia, G. G.

Publications and source records attributed to Tartaglia, G. G..

6 recordsLinked to original sources

bioRxiv2018

Insights into the structure-driven protein interactivity of RNA molecules

The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet the molecular determinants that govern interactions in protein-RNA networks are poorly known at present. Here we used the most recent experimental data to investigate the relationship between RNA structure and protein interactions. Our results show that, independently of the particular technique, the amount of structure in RNA molecules correlates with the capacity of binding to proteins in vitro and in vivo. To validate this observation, we generated an in vitro network that mimics the composition of phase-separated RNA granules. We observed that RNA, when structured, competes with protein binding and can rearrange the interaction network. The simplicity of the principle bears great potential to boost the understanding and modelling of cellular processes involving RNA-protein interactions.

molecular biology↗

bioRxiv2018

Posttranscriptional regulation of intestinal epithelial cell repair by RNA binding protein IMP1

RNA binding proteins, such as IMP1, are emerging as essential regulators of intestinal development and cancer. IMP1 hypomorphic mice exhibit severe intestinal growth defects, yet its role in adult intestinal epithelium is unclear. We employed ribosome profiling to test the effect of IMP1 loss on the \"translatome\" in colon cancer cell lines. In parallel, we evaluated mice with intestinal epithelial-specific Imp1 deletion (Imp1{Delta}IEC) following irradiation or colitis models. Ribosome-profiling revealed translation efficiency changes for multiple pathways important for intestinal homeostasis, including autophagy, in IMP1 knockout cells. We found increased autophagy flux in Imp1{Delta}IEC mice, reinforced through in silico and biochemical analyses revealing direct binding of IMP1 to autophagy transcripts MAP1LC3B and ATG3. We found that Imp1{Delta}IEC mice exhibit enhanced recovery following irradiation, which is attenuated with genetic deletion of autophagy gene Atg7. Finally, we demonstrated that IMP1 is upregulated in Crohns disease patients and Imp1 loss lessened colitis severity in mice. These studies demonstrate that IMP1 acts as a posttranscriptional regulator of gut epithelial repair post-irradiation and colitis, in part through modulation of autophagy.

physiology↗

bioRxiv2018

Insights on protein thermal stability: a graph representation of molecular interactions

Understanding the molecular mechanisms of thermal stability is a challenge in protein biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, which are intimately linked with properties of the native fold, and a wide range of potential applications from drug design to the optimization of enzyme activity.\n\nHere, we present a novel graph-theoretical framework to assess thermal stability based on the structure without any a priori information. In our approach we describe proteins as energy-weighted graphs and compare them using ensembles of interaction networks. Investigating the position of specific interactions within the 3D native structure, we developed a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and Area Under the Roc Curve of 78%.

bioinformatics↗

bioRxiv2018

Xist lncRNA forms silencing granules that induce heterochromatin formation and repressive complexes recruitment by phase separation

Main text Main text Microscopy RNA Structure Protein-RNA interactions Granule propensity Material and methods in... References Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 bases that lack coding potential1,2. They represent a significant portion of the cell transcriptome3 and work as activators or repressors of gene transcription acting on different regulatory mechanisms4-6. Indeed, lncRNAs can act as macro-scaffolds for protein recruitment7-14 and behave as guides and sponges for titrating RNA and proteins, influencing transcription at regulatory regions or triggering transcriptional interfere ...

molecular biology↗

bioRxiv2018

A method for RNA structure prediction shows evidence for structure in lncRNAs

To compare the secondary structures of RNA molecules we developed the CROSSalign method. CROSSalign is based on the combination of the Computational Recognition Of Secondary Structure (CROSS) algorithm to predict the RNA secondary structure at single-nucleotide resolution using sequence information, and the Dynamic Time Warping (DTW) method to align profiles of different lengths. We applied CROSSalign to investigate the structural conservation of long non-coding RNAs such as XIST and HOTAIR as well as ssRNA viruses including HIV. In a pool of sequences with the same secondary structure CROSSalign accurately recognizes repeat A of XIST and domain D2 of HOTAIR and outperforms other methods based on covariance modelling. CROSSalign can be applied to perform pair-wise comparisons and is able to find homologues between thousands of matches identifying the exact regions of similarity between profiles of different lengths. The algorithm is freely available at the webpage http://service.tartaglialab.com//new_submission/CROSSalign.

bioinformatics↗

bioRxiv2018

Phase Separations Driven by RNA Scaffolds and Protein Sequestration in FXTAS

Recent evidence indicates that specific RNAs promote formation of ribonucleoprotein condensates by acting as scaffolds for RNA-binding proteins (RBPs).\n\nWe systematically investigated RNA-RBP interaction networks to understand ribonucleoprotein assembly. We found that highly-contacted RNAs are highly structured, have long untranslated regions (UTRs) and contain nucleotide repeat expansions. Among the RNAs with such properties, we identified the FMR1 3 UTR that harbors CGG expansions implicated in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).\n\nWe studied FMR1 binding partners in silico and in vitro and prioritized the splicing regulator TRA2A for further characterization. In a FXTAS cellular model we validated TRA2A-FRM1 interaction and investigated implications of its sequestration at both transcriptomic and post-transcriptomic levels. We found that TRA2A co-aggregates with FMR1 in a FXTAS mouse model and in post mortem human samples.\n\nOur integrative study identifies key components of ribonucleoprotein aggregates, providing links to neurodegenerative disease and allowing the discovery of new therapeutic targets.

molecular biology↗