NF90/NF45 complexes regulate cell division

Abstract

Nuclear factor 90 (NF90) and its C‐terminally extended isoform, NF110, belong to a family of nucleic acid binding proteins. NF90/110 are isolated with the less‐studied protein NF45, as complexes interacting with highly‐structured and double‐stranded RNAs. They have been implicated in the regulation of cellular and viral genes at several levels but it remains unknown whether NF90 and NF110 form functionally distinct complexes. We studied the composition of the complexes in vivo and used siRNA strategies to elucidate their function in cells.NF90 and NF110 form heterodimeric core complexes with NF45, and large in vivo complexes in which multiple NF90/110 isoforms interact with each other. NF45 knock‐down by RNA interference led to decreased expression of NF90 and NF110. This co‐regulation is at the protein level: the stability of NF90 family proteins is dependent on binding to their NF45 partner. Reciprocally, NF90 knock‐down reduced the expression of NF45 as a result of its accelerated degradation. Cell growth is retarded and giant multi‐nucleated cells accumulate when the expression of NF45 or NF90, but not NF110, is reduced in HeLa cells. The defect leaves nuclei attached by constrictions. Thus, NF90 family members form complexes inside cells whose stability is dependent on their binding to NF45. NF90 and NF45 are essential for cell growth and their depletion results in defects in nuclei division and cytokinesis.Support: NIH AI034552