15 results match your criteria: "Centre for Human Technologies (CHT)[Affiliation]"

Rationalizing the effects of RNA modifications on protein interactions.

Mol Ther Nucleic Acids

December 2024

Centre for Human Technologies (CHT), RNA System Biology Lab, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen, 83, 16152 Genova, Italy.

RNA modifications play a crucial role in regulating gene expression by altering RNA structure and modulating interactions with RNA-binding proteins (RBPs). In this study, we explore the impact of specific RNA chemical modifications-N-methyladenosine (m⁶A), A-to-I editing, and pseudouridine (Ψ)-on RNA secondary structure and protein-RNA interactions. Utilizing genome-wide data, including RNA secondary structure predictions and protein-RNA interaction datasets, we classify proteins into distinct categories based on their binding behaviors: modification specific and structure independent, or modification unspecific and structure dependent.

View Article and Find Full Text PDF

Investigating the binding between proteins and aptamers, such as peptides or RNA molecules, is of crucial importance both for understanding the molecular mechanisms that regulate cellular activities and for therapeutic applications in several pathologies. Here, a new computational procedure, employing mainly docking, clustering analysis, and molecular dynamics simulations, was designed to estimate the binding affinities between a protein and some RNA aptamers, through the investigation of the dynamical behavior of the predicted molecular complex. Using the state-of-the-art software catRAPID, we computationally designed a set of RNA aptamers interacting with the TAR DNA-binding protein 43 (TDP-43), a protein associated with several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).

View Article and Find Full Text PDF

Structure-based mechanism of riboregulation of the metabolic enzyme SHMT1.

Mol Cell

July 2024

Department of Biochemical Sciences, Sapienza University of Rome, P. le Aldo Moro 5, 00185 Rome, Italy; Department of Biochemical Sciences, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, P.le A. Moro 5, 00185 Rome, Italy. Electronic address:

RNA can directly control protein activity in a process called riboregulation; only a few mechanisms of riboregulation have been described in detail, none of which have been characterized on structural grounds. Here, we present a comprehensive structural, functional, and phylogenetic analysis of riboregulation of cytosolic serine hydroxymethyltransferase (SHMT1), the enzyme interconverting serine and glycine in one-carbon metabolism. We have determined the cryoelectron microscopy (cryo-EM) structure of human SHMT1 in its free- and RNA-bound states, and we show that the RNA modulator competes with polyglutamylated folates and acts as an allosteric switch, selectively altering the enzyme's reactivity vs.

View Article and Find Full Text PDF

The combination of morphogenetic and transcription factors together with the synergic aid of noncoding RNAs and their cognate RNA binding proteins contribute to shape motor neurons (MN) identity. Here, we extend the noncoding perspective of human MN, by detailing the molecular and biological activity of CyCoNP (as Cytoplasmic Coordinator of Neural Progenitors) a highly expressed and MN-enriched human lncRNA. Through in silico prediction, in vivo RNA purification and loss of function experiments followed by RNA-sequencing, we found that CyCoNP sustains a specific neuron differentiation program, required for the physiology of both neuroblastoma cells and hiPSC-derived MN, which mainly involves miR-4492 and NCAM1 mRNA.

View Article and Find Full Text PDF

RNA-binding proteins are central for many biological processes and their characterization has demonstrated a broad range of functions as well as a wide spectrum of target structures. RNA G-quadruplexes are important regulatory elements occurring in both coding and non-coding transcripts, yet our knowledge of their structure-based interactions is at present limited. Here, using theoretical predictions and experimental approaches, we show that many chromatin-binding proteins bind to RNA G-quadruplexes, and we classify them based on their RNA G-quadruplex-binding potential.

View Article and Find Full Text PDF
Article Synopsis
  • Protein misfolding and aggregation into complex structures are common in neurodegenerative diseases, affecting conditions like Parkinson's.
  • Single-molecule techniques have improved the study of these rare protein aggregates, but they often require tagged proteins or non-specific dyes.
  • The researchers developed a method using high-affinity antibodies and advanced microscopy to specifically detect α-synuclein aggregates in low concentrations within biological samples.
View Article and Find Full Text PDF

Prediction of protein-RNA interactions from single-cell transcriptomic data.

Nucleic Acids Res

April 2024

Center for Life Nano- and Neuro-Science, RNA Systems Biology Lab, Fondazione Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy.

Proteins are crucial in regulating every aspect of RNA life, yet understanding their interactions with coding and noncoding RNAs remains limited. Experimental studies are typically restricted to a small number of cell lines and a limited set of RNA-binding proteins (RBPs). Although computational methods based on physico-chemical principles can predict protein-RNA interactions accurately, they often lack the ability to consider cell-type-specific gene expression and the broader context of gene regulatory networks (GRNs).

View Article and Find Full Text PDF

The development of methods able to modulate the binding affinity between proteins and peptides is of paramount biotechnological interest in view of a vast range of applications that imply designed polypeptides capable to impair or favour Protein-Protein Interactions. Here, we applied a peptide design algorithm based on shape complementarity optimization and electrostatic compatibility and provided the first experimental proof of the efficacy of the design algorithm. Focusing on the interaction between the SARS-CoV-2 Spike Receptor-Binding Domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor, we extracted a 23-residues long peptide that structurally mimics the major interacting portion of the ACE2 receptor and designed five mutants of such a peptide with a modulated affinity.

View Article and Find Full Text PDF

It is not well understood why severe acute respiratory syndrome (SARS)-CoV-2 spreads much faster than other β-coronaviruses such as SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. In a previous publication, we predicted the binding of the N-terminal domain (NTD) of SARS-CoV-2 spike to sialic acids (SAs). Here, we experimentally validate this interaction and present simulations that reveal a second possible interaction between SAs and the spike protein via a binding site located in the receptor-binding domain (RBD).

View Article and Find Full Text PDF
Article Synopsis
  • SARS-CoV-2, a virus responsible for COVID-19, interacts with host cell proteins to both inhibit and promote its own replication, yet many of these interactions remain unclear.
  • Researchers used advanced techniques to identify host proteins that specifically bind to crucial regions of the SARS-CoV-2 RNA, focusing on a protein called PUS7.
  • Their findings reveal significant post-transcriptional modifications in the viral RNA and suggest that understanding these interactions could lead to new treatment strategies for COVID-19.
View Article and Find Full Text PDF

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a large multi-spanning membrane protein that is susceptible to misfolding and aggregation. We have identified here the region responsible for this instability. Temperature-induced aggregation of C-terminally truncated versions of CFTR demonstrated that all truncations up to the second transmembrane domain (TMD2), including the R region, largely resisted aggregation.

View Article and Find Full Text PDF

RNA sequestration driven by amyloid formation: the alpha synuclein case.

Nucleic Acids Res

November 2023

Centre for Human Technologies (CHT), Istituto Italiano di Tecnologia (IIT), Via Enrico Melen, 83, 16152, Genova, Italy.

Article Synopsis
  • - Nucleic acids, particularly RNA, can either help or hinder how proteins aggregate, depending on the specific conditions they are in.
  • - The study used computational methods to analyze properties of regions in proteins that are involved in amyloid aggregation, finding that outer regions of these proteins are disordered and tend to interact with nucleic acids.
  • - Experimental tests with alpha-synuclein proteins showed that adding RNA sped up aggregation, especially with a mutant version that has a stronger affinity for RNA, suggesting a common link between RNA sequestration and protein aggregation.
View Article and Find Full Text PDF

FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation.

Int J Mol Sci

February 2023

Department of Pharmaceutical Sciences, Department of Excellence 2018-2022, University of Perugia, 06123 Perugia, Italy.

Deregulation of RNA metabolism has emerged as one of the key events leading to the degeneration of motor neurons (MNs) in Amyotrophic Lateral Sclerosis (ALS) disease. Indeed, mutations on RNA-binding proteins (RBPs) or on proteins involved in aspects of RNA metabolism account for the majority of familiar forms of ALS. In particular, the impact of the ALS-linked mutations of the RBP FUS on many aspects of RNA-related processes has been vastly investigated.

View Article and Find Full Text PDF
Article Synopsis
  • Protein misfolding and aggregation into structures like oligomers and fibrils are linked to various neurodegenerative diseases.
  • Traditional methods for studying these aggregates often lack specificity and rely on labeled proteins or non-specific stains.
  • The researchers developed a new technique using a high-affinity antibody with unique fluorophores and advanced microscopy to specifically identify and analyze α-synuclein aggregates in low concentrations, relevant to biological samples.
View Article and Find Full Text PDF

Aptamers are artificial oligonucleotides binding to specific molecular targets. They have a promising role in therapeutics and diagnostics but are often difficult to design. Here, we exploited the catRAPID algorithm to generate aptamers targeting TAR DNA-binding protein 43 (TDP-43), whose aggregation is associated with Amyotrophic Lateral Sclerosis.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: