Melikishvili Manana, De Silva Kalpani, Chandler Darrell P, Cassidy Richard N, Andreeva Kalina, Dhahri Hejer, Rouchka Eric C, Fondufe-Mittendorf Yvonne N
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA.
Department of Neuroscience Training, University of Louisville, Louisville, KY 40292, USA.
iScience. 2025 Aug 6;28(9):113299. doi: 10.1016/j.isci.2025.113299. eCollection 2025 Sep 19.
Recent discoveries showed that some chromatin-binding proteins also interact with RNA to regulate gene expression. Poly (ADP-ribose) polymerase 1 (PARP1) and methyl-CpG binding protein 2 (MeCP2) are two chromatin-associated, DNA-binding proteins that play central roles in gene expression, DNA damage response, and epigenetic regulation. Both proteins possess RNA-binding properties, but the mechanism by which PARP1 and MeCP2 recognize RNA-binding sites remains unclear. Using a systematic evolution of ligands by exponential enrichment (SELEX) approach with a random 70-mer RNA library, we uncovered that PARP1 preferentially binds guanine-rich RNAs, while MeCP2 favors cytosine-rich targets. However, neither protein recognizes a consensus (linear) RNA sequence motif. Instead, PARP1 targets RNAs with long stems and small loops, while MeCP2 targets RNAs with large loops or bulges and intricate multi-stem structures. These findings suggest that both proteins rely on distinct RNA structural features, highlighting the structural versatility of RNA as a regulatory element.
最近的研究发现表明，一些染色质结合蛋白也与RNA相互作用以调控基因表达。聚（ADP-核糖）聚合酶1（PARP1）和甲基-CpG结合蛋白2（MeCP2）是两种与染色质相关的DNA结合蛋白，它们在基因表达、DNA损伤反应和表观遗传调控中发挥着核心作用。这两种蛋白都具有RNA结合特性，但PARP1和MeCP2识别RNA结合位点的机制仍不清楚。通过使用指数富集的配体系统进化（SELEX）方法和一个随机的70聚体RNA文库，我们发现PARP1优先结合富含鸟嘌呤的RNA，而MeCP2则倾向于富含胞嘧啶的靶标。然而，这两种蛋白都不识别一致（线性）的RNA序列基序。相反，PARP1靶向具有长茎和小环的RNA，而MeCP2靶向具有大环或凸起以及复杂多茎结构的RNA。这些发现表明这两种蛋白都依赖于不同的RNA结构特征，突出了RNA作为调控元件的结构多样性。
