Dr Florent Hubé

Florent Hubé
Team “Transgenerational Epigenetics & small RNA Biology” UMR7622 Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine

Title:
Two families of snoRNAs rescue myogenic differentiation via pseudourylation of CyclinD3 mRNA

Abstract:
Recently, the repertoire of human small nucleolar noncoding RNAs (snoRNAs) and their potential functions has expanded with the identification of new snoRNAs and additional messenger RNA (mRNA) targets. snoRNA-guided modifications may influence mRNA stability, translation, and splicing. In previous work, we identified snoRNAs that are highly expressed in healthy human muscle progenitor cells. In this study, we show that loss of SNORA40 and SNORA70 impairs myogenic differentiation, while their gain of function can rescue differentiation defects in muscle progenitor cells from individuals with myotonic dystrophy type 1 (DM1). We identified cyclin D3 (CCND3) mRNA—partially localized in the nucleolus—as a target of SNORA40 and SNORA70, which are required for its pseudouridylation. CCND3 protein expression is essential for muscle progenitor cells to exit the cell cycle upon induction of differentiation, and we demonstrate that this transition depends on SNORA40/70. We further observed that DM1 cells exhibit reduced levels of SNORA40/70 and lack detectable CCND3 protein. Restoring normal levels of SNORA40/70 partially reinstated CCND3 protein expression and improved the fusion capacity of DM1 muscle progenitors. Collectively, these findings suggest that SNORA40/70-dependent pseudouridylation of CCND3 mRNA underlies these effects, highlighting snoRNAs as key regulators of both normal and pathological muscle differentiation.enerations.