Biology subjects

Buonaiuto, G.

Publications and source records attributed to Buonaiuto, G..

4 recordsLinked to original sources

bioRxiv2024

Long noncoding RNA HSCHARME promotes the maturation of stem cells-derived cardiomyocytes by controlling gene regulatory networks altered in human cardiomyopathies

A growing body of evidence suggests that tissue-specific long noncoding RNAs (lncRNA) play pivotal roles in the heart. Here, we exploited the synteny between the mouse and human genomes to identify the novel lncRNA HSCHARME (Human Syntenic CHARME) and combined single-cell transcriptomics, CAGE-seq data, RNA-FISH imaging and CRISPR-Cas9 genome editing to document its role in cardiomyogenesis. By investigating the mechanism of action of HSCHARME in hiPSC-derived cardiomyocytes, we found that the locus produces the major pCHARME isoform that associates with SC35-containing speckles and interacts with the splicing regulator PTBP1. Consistently, the functional inactivation of pCHARME influences the splicing of cardiac-specific pre-mRNAs and impacts their expression, which parallels a decline in cardiomyocyte differentiation and physiology. In line with a possible association with disease, large-scale analysis of the lncRNA expression across cardiomyopathy patients revealed increased levels of pCHARME in hypertrophic (HCM) and dilated (DCM) hearts and identified a subset of disease-associated targets whose expression can be modulated through HSCHARME dosage. By unlocking mechanistic insights into the role of pCHARME in cardiac cells, our data identify a novel non-coding regulator of cardiomyocyte function with potential implications in disease.

molecular biology↗

bioRxiv2024

Genome biology of long non-coding RNAs in humans: a virtual karyotype

BackgroundLong non-coding RNAs (lncRNAs) represent a unique and groundbreaking class of RNA molecules that exert regulatory functions with remarkable tissue and cellular specificities. Although the number of identified functional lncRNAs is increasing, comprehensive profiling of lncRNA genomics remains elusive. Creating a virtual lncRNA karyotype is especially important for species whose intrinsic features enable their biosynthesis and function in context-dependent manners. Results and conclusionsTo address this challenge, we employed existing annotation files to create a statistical genomics portrait of lncRNA genes for comparison with protein-coding genes. We provide a foundational reference for exploring the non-coding genome, offering insights into the genomic characteristics of lncRNAs that may enhance understanding of their biological significance and impact.

genomics↗

bioRxiv2022

The long noncoding RNA Charme supervises cardiomyocytes maturation by controlling cell differentiation programs in the developing heart

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes-of-action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodelling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing and whole-mount in situ hybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the myocardium and ventricular hypo-trabeculation. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications.

molecular biology↗

bioRxiv2020

Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA lnc-Rewind in muscle stem cells

Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cells (MuSCs) activity. This ability requires the proper balance between MuSCs expansion and differentiation which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated lncRNA, lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, lnc-Rewind acts as an epigenetic regulator of MuSCs proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct lnc-Rewind target. We show that lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.

cell biology↗