ELYS coordinates NF-κB pathway dynamics during development inDrosophila

Summary Statement ELYS, a nucleoporin spatiotemporally regulates NF-κB pathway dynamics during development in Drosophila and its misregulation in post-embryonic stages leads to apoptosis mediated abnormalities. 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 ( d Elys) plays critical roles during Drosophila development. Through in silico analyses, we find all conserved structural features in d Elys except for the presence of non-canonical AT-hook motif strongly binding with DNA. d Elys localized to nuclear rim in interphase cells, but during mitosis, it was present on chromatin. RNAi mediated depletion of d Elys leads to aberrant development and defects in the nuclear lamina and NPCs assembly at the cellular level. Furthermore, we demonstrate that in d Elys depletion NF-κB is activated and accumulates inside the nucleus which results in illimed expression of critical molecules. d Elys depletion sustains NF-κB into the nucleus in post-embryonic stages. Prolonged NF-κB inside nucleus induces apoptosis in response to hitherto unknown quality check mechanism and highlights on the under-appreciated apoptotic paradigm of NF-κB pathway.