Central Role of the lnc-RNA xsc-1 in Meiosis, Meiotic Sex Chromosome Inactivation, and in Genome Stability
AWARD NOMINEE

Introduction

Long non-coding RNAs (lncRNAs) play crucial roles in controlling developmental and differentiation processes. The transparent nematode c. elegans is an outstanding model for basic research of the meiotic processes, since cells throughout the meiotic stages are organized in a spatio-temporal manner.

Aim

We aim to study the role and importance of lncRNAs during the conserved process of meiosis and their role in fertility and reproduction.

Materials & Methods

We used CRISPR/Cas9 system to delete the entire sequence of the lncRNA xsc-1 gene of the nematode, followed by whole-genome sequencing to ensure the absence of off-targets mutations. Then, we tested the reproductive features of the mutated worms. Impact on meiotic cells and chromosome segregation was examined by immunostaining. Full transcriptome was sequenced for analyzing differential gene expression in worms lacking the xsc-1 gene.

Results

Mutated worms demonstrated several phenotypes including severe meiotic defects; Mutants’ brood size was 50% smaller compared to WT, and 40% of laid eggs didn`t hatch. DAPI staining revealed that most of mutants’ oocytes had chromosomal aberrations including chromosomal aggregates and fragments. Immunostaining revealed perturbations in DNA repair of meiocytes. Immunostaining and transcriptome analysis revealed that the inactivation of X chromosomes in the early stages of oogenesis was significantly decreased in the mutants.

Conclusions

We hypothesize that xsc-1 is involved in X chromosome control in the germline and through this mechanism plays an important role in meiosis and genome stability. These findings can open a window to understanding the involvement and impact of lnc-RNAs on fertility.