RT Journal Article
SR Electronic
T1 Structural features within the NORAD long noncoding RNA underlie efficient repression of Pumilio activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.19.469243
DO 10.1101/2021.11.19.469243
A1 Omer Ziv
A1 Svetlana Farberov
A1 Jian You Lau
A1 Eric Miska
A1 Grzegorz Kudla
A1 Igor Ulitsky
YR 2021
UL http://biorxiv.org/content/early/2021/11/19/2021.11.19.469243.abstract
AB It is increasingly appreciated that long non-coding RNAs (lncRNAs) carry out important functions in mammalian cells, but how these are encoded in their sequences and manifested in their structures remains largely unknown. Some lncRNAs bind to and modulate the availability of RNA binding proteins, but the structural principles that underlie this mode of regulation are underexplored. Here, we focused on the NORAD lncRNA, which binds Pumilio proteins and modulates their ability to repress hundreds of mRNA targets. We probed the RNA structure and long-range RNA-RNA interactions formed by NORAD inside cells, under different stressful conditions. We discovered that NORAD structure is highly modular, and consists of well-defined domains that contribute independently to NORAD function. We discovered that NORAD structure spatially clusters the Pumilio binding sites along NORAD in a manner that contributes to the de-repression of Pumilio target proteins. Following arsenite stress, the majority of NORAD structure undergoes relaxation and forms inter-molecular interactions with RNAs that are targeted to stress granules. NORAD sequence thus dictates elaborated structural domain organization that facilitates its function on multiple levels, and which helps explain the extensive evolutionary sequence conservation of NORAD regions that are not predicted to directly bind Pumilio proteins.Competing Interest StatementThe authors have declared no competing interest.