Interactions of a Long Noncoding RNA with Domains of NF-κB and IκBα: Implications for the Inhibition of Non-Signal-Related Phosphorylation.
Interactions of a Long Noncoding RNA with Domains of NF-κB and IκBα: Implications for the Inhibition of Non-Signal-Related Phosphorylation.
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DOI：
10.1021/acs.biochem.1c00732
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发表时间：
2022-03-01
期刊：
影响因子：
2.9
通讯作者：
Dyson HJ
中科院分区：
文献类型：
--
作者：
Singh A;Martinez-Yamout MA;Wright PE;Dyson HJ
转录因子NF-κB是细胞信号传导途径的中心介质之一。在静息条件下，典型的RelA-p50（p65-p50）异源二聚体NF-κB与其抑制剂IκBα复合物保持隔离在细胞质中。信号介导的NF-κB的活化涉及IκBα的磷酸化、泛素化和降解以及NF-κB向细胞核的移位。最近研究表明，一种长链非编码RNA（NKILA）可以通过与细胞质中的NF-κB-IκBα复合物相互作用来调节NF-κB信号通路。在本研究中，我们使用NMR光谱和天然凝胶电泳研究了NKILA衍生的RNA序列与NF-κB和IκBα结构域的相互作用。我们的研究结果表明，两个RNA发夹序列与RelA（p65）和p50的Rel同源区的DNA结合结构域相互作用，并且在低盐条件下，相同的RNA序列可以影响IκBα N-末端的磷酸化。我们还观察到全长RHR二聚体（p65和p50的异源二聚体和p50的同源二聚体）与RNA发夹的相互作用比NF-κB的单个结构域更强。我们观察到的NKILA片段与NF-κB结构域之间的所有相互作用均较弱且非特异性，与NKILA-NF-κB-IκBα相互作用在保护NFκB-I κ Bα复合物免受NF-κB信号通路异常激活中的预期功能一致。
The transcription factor NF-κB is one of the central mediators of cellular signaling pathways. Under resting conditions, the canonical RelA-p50 (p65-p50) heterodimer NF-κB remains sequestered in the cytoplasm in complex with its inhibitor IκBα. Signal-mediated activation of NF-κB involves phosphorylation, ubiquitination and degradation of IκBα, and translocation of NF-κB to the nucleus. It was recently shown that a long non-coding RNA (termed NKILA) can modulate the NF-κB signaling circuit by interacting with the NF-κB-IκBα complex in the cytoplasm. In the current study, we investigated the interaction of RNA sequences derived from NKILA with domains of NF-κB and IκBα using NMR spectroscopy and native gel electrophoresis. Our results indicate that two RNA hairpin sequences interact with the DNA-binding domains of the Rel homology regions of RelA (p65) and p50, and that the same RNA sequences can affect the phosphorylation of the N-terminus of IκBα under low-salt conditions. We also observe that full-length RHR dimers (heterodimer of p65 and p50 and homodimer of p50) show a stronger interaction with the RNA hairpins than the individual domains of NF-κB. All of the interactions we observe between fragments of NKILA and domains of NF-κB are weak and non-specific, consistent with the proposed function of the NKILA-NF-κB-IκBα interaction in protecting the NFκB-IκBα complex from aberrant activation of the NF-κB signaling pathway.
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影响因子：
14.9
作者：
Hart, DJ;Speight, RE;Blackburn, JM
通讯作者：
Blackburn, JM
影响因子：
2.9
作者：
Vranken, WF;Boucher, W;Laue, ED
通讯作者：
Laue, ED
影响因子：
64.8
作者：
GHOSH, G;VANDUYNE, G;SIGLER, PB
通讯作者：
SIGLER, PB
DOI：
10.1186/s13046-017-0518-0
发表时间：
2017-04-17
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Lu Z;Li Y;Wang J;Che Y;Sun S;Huang J;Chen Z;He J
通讯作者：
He J
影响因子：
5.6
作者：
Lin, Su-Chang;Chung, Jee Y.;Wu, Hao
通讯作者：
Wu, Hao