Andrea Schorn

‘Mobile genes’ or transposable elements, which are closely related to viruses, promote active gene expression in a selfish manner. These elements are usually buried in inactive, condensed DNA by their host to prevent mutagenic damage. However, both stem cells in the embryo and cancer cells undergo genome-wide reprogramming that re-activates silent transposable elements. My lab is exploring how the host recognizes transposons amongst thousands of genes and non-coding DNA and specifically restricts transposon mobility.

We found that a highly conserved 18 nucleotide sequence motif is the Achille’s heel of a wide-spread class of transposable elements that are closely related to retroviruses such as HIV. These retroelements initiate replication at the 18 nucleotide binding site using transfer RNA (tRNA), an essential RNA component of the cell. In turn, cells produce short fragments of tRNAs that we discovered inhibit this class of retroelements. These tRNA fragments are processed from mature tRNAs under yet unknown conditions and potentially protect many cell types in eukaryotes. We are investigating under which conditions cells produce this class of small RNAs and assessing their impact on development and pluripotency. tRNA fragments are an ancient link between the ‘RNA interference’ silencing machinery, transposons and genome stability, with potential roles in trans-generational inheritance and cancer.