ELYS coordinates NF-κB pathway dynamics during development inDrosophila

Abstract

Nuclear pores are the exclusive conduit to facilitate the nucleocytoplasmic transport in a precisely regulated manner. ELYS, a constituent protein of nuclear pores, initiates assembly of nuclear pore complexes (NPCs) into functional nuclear pores towards the end of mitosis. Using cellular, molecular and genetic tools, here, we report that ELYS orthologue (dElys) plays critical roles during Drosophila development. Through in silico analyses, we find all conserved structural features in dElys except for the presence of non-canonical AT-hook motif strongly binding with DNA. dElys localized to nuclear rim in interphase cells, but during mitosis, it was present on chromatin. RNAi mediated depletion of dElys leads to aberrant development and defects in the nuclear lamina and NPCs assembly at the cellular level. Furthermore, we demonstrate that in dElys depletion NF-B is activated and accumulates inside the nucleus which results in illtimed expression of critical molecules. dElys depletion sustains NF-B into the nucleus in post-embryonic stages. Prolonged NF-B inside nucleus induces apoptosis in response to hitherto unknown quality check mechanism and highlights on the underappreciated apoptotic paradigm of NF-B pathway.