Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
Biochemistry. 2013 Dec 31;52(52):9519-27. doi: 10.1021/bi401085h. Epub 2013 Dec 17.
Long noncoding RNAs (lncRNAs) play a key role in the epigenetic regulation of cells. Many of these lncRNAs function by interacting with histone repressive proteins of the Polycomb group (PcG) family, recruiting them to gene loci to facilitate silencing. Although there are now many RNAs known to interact with the PRC2 complex, little is known about the details of the molecular interactions. Here, we show that the PcG protein heterodimer EZH2-EED is necessary and sufficient for binding to the lncRNA HOTAIR. We also show that protein recognition occurs within a folded 89-mer domain of HOTAIR. This 89-mer represents a minimal binding motif, as further deletion of nucleotides results in substantial loss of affinity for PRC2. These findings provide molecular insights into an important system involved in epigenetic regulation.
长链非编码 RNA（lncRNA）在细胞的表观遗传调控中发挥着关键作用。这些 lncRNA 中的许多通过与多梳抑制复合物（PcG）家族的组蛋白抑制蛋白相互作用来发挥功能，将它们招募到基因座以促进沉默。尽管现在已经有许多已知与 PRC2 复合物相互作用的 RNA，但对于分子相互作用的细节知之甚少。在这里，我们表明 PcG 蛋白异二聚体 EZH2-EED 对于与 lncRNA HOTAIR 的结合是必需且充分的。我们还表明，蛋白识别发生在 HOTAIR 的折叠 89 -mer 结构域内。这个 89-mer 代表一个最小的结合基序，因为进一步缺失核苷酸会导致对 PRC2 的亲和力显著降低。这些发现为参与表观遗传调控的重要系统提供了分子见解。
