A 36-base hairpin within lncRNA DRAIC, which is modulated by alternative splicing, interacts with the IKKα coiled-coil domain and inhibits NF-κB and tumor cell phenotypes.

ABSTRACT: A tumor-suppressive long-noncoding RNA (lncRNA) DRAIC (downregulated RNAin cancers) inhibits NF-κB activity and physically interacts with IKKα, a kinase component of the IKK complex, in several cancer types. Here we explore the precise molecular mechanism involved in this interaction and suppression. Using SHAPE-MaP, we identified a 36-nucleotide hairpin (A + B) within DRAIC that is necessary and sufficient for its anti-oncogenic function. RNA immunoprecipitation (RIP) and Electrophoretic mobility shift assays (EMSA) confirmed that this hairpin physically interacts with the coiled coil domain of IKKα. A + B RNA has a high-binding affinity (KD ∼1-7 nM) to IKKα. The binding of A + B disrupts the dimerization of NEMO and IKKα coiled-coil domains, a critical step for IKK action. Consistent wit

SUBMITTER: Hao X 

PROVIDER: S-EPMC12205651 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature