RT Journal Article SR Electronic T1 PUMILIO, but not RBMX, binding is required for regulation of genomic stability by noncoding RNA NORAD JF bioRxiv FD Cold Spring Harbor Laboratory SP 645960 DO 10.1101/645960 A1 Mahmoud M. Elguindy A1 Florian Kopp A1 Mohammad Goodarzi A1 Frederick Rehfeld A1 Anu Thomas A1 Tsung-Cheng Chang A1 Joshua T. Mendell YR 2019 UL http://biorxiv.org/content/early/2019/05/22/645960.abstract AB NORAD is a highly-conserved and abundant long noncoding RNA (lncRNA) that is required for maintenance of genomic stability in mammals. Although initial characterization of NORAD established it as a negative regulator of PUMILIO (PUM) proteins in the cytoplasm, a nuclear role for NORAD in genome maintenance through an interaction with the RNA binding protein RBMX has also been reported. Here we addressed the relative contributions of NORAD:PUM and NORAD:RBMX interactions to the regulation of genomic stability by this lncRNA. Extensive RNA FISH and fractionation experiments established that NORAD 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 NORAD whereas binding of RBMX is dispensable for this function. These data therefore establish an essential role for the NORAD:PUM interaction in genome maintenance and provide a foundation for further mechanistic dissection of this pathway.