One crucial part of human cells is a structure called the nuclear envelope, which surrounds the cell nucleus – home to our DNA. This structure is essential for maintaining normal nuclear architecture and cell function. Dysfunction of the nuclear envelope leads to various human diseases, including the rare, but devastating Hutchinson-Gilford progeria syndrome (HGPS) for which there is no current cure. In their new publication, Professor Steve Jackson’s Group at the Wellcome Trust Gurdon Institute and Dr Delphine Larrieu’s Group at the Cambridge Institute for Medical Research identified a new pathway – the Transportin-1 pathway responsible for importing several proteins into the nucleus – as being affected in HGPS. These proteins are involved in important cellular processes including organisation of DNA structure and regulation of gene expression. Consequently, in HGPS, they cannot effectively reach the nucleus and are therefore unable to play their normal roles. The authors show that by targeting a protein called NAT10, we can restore the Transportin-1 pathway in HGPS cells, leading to improvement of DNA structure, gene expression re-balancing, and delayed entry of cells into senescence.
