Ricerc@Sapienza

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of children and adolescents. The fusion-positive (FP)-RMS variant expressing chimeric oncoproteins such as PAX3-FOXO1 and PAX7-FOXO1 is at high risk. The fusion negative subgroup, FN-RMS, has a good prognosis when non-metastatic. Despite a multimodal therapeutic approach, FP-RMS and metastatic FN-RMS often show a dismal prognosis with 5-year survival of less than 30%. Therefore, novel targets need to be discovered to develop therapies that halt tumor progression, reducing long-term side effects in young patients.

Vasopressin (arg8-vasopressin) and oxytocin are closely relalated hormones, synthesized as pre-hormones in the magnocellular neurons of the paraventricular Q6
and supraoptic nuclei of the hypothalamus. Vasopressin and oxytocin are secreted in response to a variety of physiological stimuli, serving such different functions as controlling water balance, milk ejection, uterine contraction, mood, and parental behavior (Lechan and Toni, 2000; Costa et al., 2014a).

Desideri et al. study the role of the chromatin-retained isoform of Charme, a lncRNA that regulates myogenesis. They find that a MATR3/PTBP1/pCharme assembly drives the retention and the function of the lncRNA. CRISPR-Cas9 deletion of pCharme intron-1 leads to the transcript delocalization and to heart defects in vivo.

Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and miRNAs, long noncoding RNAs (lncRNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin-associated muscle-specific lncRNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo. In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein.

Cytoplasmic long non-coding RNAs have been shown to act at many different levels to control post-transcriptional gene expression, although their role in translational control is poorly understood. Here, we show that lnc-31, a non-coding RNA required for myoblast proliferation, promotes ROCK1 protein synthesis by stabilizing its translational activator, YB-1. We find that lnc-31 binds to the Rock1 mRNA as well as to the YB-1 protein and that translational activation requires physical interaction between the two RNA species.

In 1957, Francis Crick speculated that RNA, beyond its protein-coding capacity, could have its own function. Decade after decade this theory was dramatically boosted by the discovery of new classes of noncoding RNAs (ncRNAs), including long noncoding (lnc)RNAs and circular (circ)RNAs, which play a fundamental role in the fine spatio-temporal control of multiple layers of gene expression. Recently, many of these molecules have been identified in a plethora of different tissues and they have emerged to be more cell type specific than protein coding genes.

Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy.