Our research axes

Using the fission yeast Schizosaccharomyces pombe (S. pombe) and human cell lines as evolutionarily distant model systems, we investigate the potentially conserved role, mode of action and regulation of noncoding RNAs (ncRNAs) and their producing transcription in the context of pericentromeric heterochromatin. Our original studies in S. pombe highlighted a conserved function of RNAs in nucleating heterochromatin formation and heterochromatin gene silencing at different genomic sites. In our ongoing work, we are investigating the conservation of this function at human pericentromeric regions and exploring other novel molecular functions of ncRNAs. In parallel, our recent work in human has shed light on another key role of pericentromeric ncRNAs in reprogramming genome expression.

By focusing on nuclear members of the conserved family of YTH RNA binding proteins and the cell response to various stresses, we are investigating the role of transcripts (ncRNAs and mRNAs) and their internal methylation (m6A, which is specifically recognized by the YTH proteins) in controlling gene expression by acting in the environment of both heterochromatin and euchromatin. Our work has uncovered that Mmi1 YTH protein drives a novel chromatin- and ncRNA-dependent mechanism that controls S. pombe entry into sexual differentiation induced by metabolic stress (i.e., nutrient starvation). Our ongoing work is investigating the potential conservation of Mmi1-driven gene silencing mechanisms in human cells by exploring where, when, and how the association of YTHDC1 YTH protein (which is the functional analog of S. pombe Mmi1) contributes to chromatin- and RNA-associated gene regulation in response to heat stress.