PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA .

is a conserved long noncoding RNA (lncRNA) that is required for genome stability in mammals. acts as a negative regulator of PUMILIO (PUM) proteins in the cytoplasm, and we previously showed that loss of or PUM hyperactivity results in genome instability and premature aging in mice (Kopp et al., 2019). Recently, however, it was reported that regulates genome stability through an interaction with the RNA binding protein RBMX in the nucleus. Here, we addressed the contributions of :PUM and :RBMX interactions to genome maintenance by this lncRNA in human cells. Extensive RNA FISH and fractionation experiments established that localizes predominantly to the cytoplasm with or without DNA damage. Moreover, genetic rescue experiments demonstrated that PUM binding is required for maintenance of genomic stability by whereas binding of RBMX is dispensable for this function. These data provide an important foundation for further mechanistic dissection of the -PUMILIO axis in genome maintenance.