Project 24.3

I am fascinated by the role of long non-coding RNAs (lncRNAs) in developmental gene regulation. My project focuses on ANTSR, a newly discovered lncRNA that promotes female development in the Argentine ant. I aim to uncover the sex-specific transcriptional activity of ANTSR and how it functions at the molecular level, offering insights into how lncRNAs can act as master regulators in insect development.

Sex determination is a crucial developmental process, yet its molecular underpinnings remain poorly understood in most non-model organisms. Long non-coding RNAs (lncRNAs) have emerged as important regulators of gene expression and developmental pathways, including sex determination (Valsecchi et al. 2021; Wittkopp et al. 2024). In the Argentine ant (Linepithema humile), a recent study identified ANTSR, a lncRNA-encoding gene, as a putative master regulator of female development (Pan et al. 2024).

Expression of ANTSR is strongly associated with heterozygosity at a hyper-polymorphic genomic region. Heterozygous embryos exhibit high ANTSR expression and develop into females, whereas homozygous or hemizygous embryos show low or no expression and develop into males (Pan et al. 2024). While this pattern is analogous to the complementary sex determination (CSD) system of honeybees—where sex is determined by allelic diversity at the csd locus (Otte et al. 2023)—the underlying gene in ants is a non-coding RNA rather than a protein-coding gene.

Despite its apparent centrality to female development, the regulatory mechanisms governing ANTSR expression and the molecular function of the lncRNA transcript itself remain entirely unknown. This project aims to fill this gap by comprehensively characterizing the transcriptional activity of ANTSR across various developmental contexts, identifying potential interaction partners (RNA, DNA, or protein), and elucidating its role in sex-specific developmental pathways.

To address these questions, we will combine molecular biology techniques and transcriptomic analyses to uncover the mechanistic basis of ANTSR activity. By focusing specifically on ANTSR, this research will provide a new perspective on how lncRNAs can function as sex-determining signals in insects and lay the foundation for future investigations into the evolution and diversification of genetic sex determination systems.

References

Keller Valsecchi CI, Basilicata MF, et al. (2021) RNA Nucleation by MSL2 Induces Selective X Chromosome Compartmentalization. Nature 589 (7840): 137–42. https://www.nature.com/articles/s41586-020-2935-z

Otte M, Netschitailo O, Weidtkamp-Peters S, Seidel CAMl, Beye M (2023) Recognition of Polymorphic Csd Proteins Determines Sex in the Honeybee. Science Advances 9 (40): eadg4239. doi.org/10.1126/sciadv.adg4239

Pan Q, Darras H, Keller L (2024) LncRNA Gene ANTSR Coordinates Complementary Sex Determination in the Argentine Ant. Science Advances 10(22): adp1532. doi.org/10.1126/sciadv.adp1532

Wittkopp N, Jesus Domingues AM, Ketting RF (2024) miR214 Regulates Sex Determination through Gsdf in Zebrafish. bioRxiv. doi.org/10.1101/2024.05.01.592007