Institute of Enzymology, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary.
Doctoral School of Biology, Institute of Biology, ELTE Eötvös Loránd University, H-1117 Budapest, Hungary.
Int J Mol Sci. 2023 Nov 7;24(22):16032. doi: 10.3390/ijms242216032.
For several histone lysine methyltransferases (HKMTs), RNA binding has been already shown to be a functionally relevant feature, but detailed information on the RNA interactome of these proteins is not always known. Of the six human KMT2 proteins responsible for the methylation of the H3K4 residue, two-SETD1A and SETD1B-contain RNA recognition domains (RRMs). Here we investigated the RNA binding capacity of SETD1A and identified a broad range of interacting RNAs within HEK293T cells. Our analysis revealed that similar to yeast Set1, SETD1A is also capable of binding several coding and non-coding RNAs, including RNA species related to RNA processing. We also show direct RNA binding activity of the individual RRM domain in vitro, which is in contrast with the RRM domain found in yeast Set1. Structural modeling revealed important details on the possible RNA recognition mode of SETD1A and highlighted some fundamental differences between SETD1A and Set1, explaining the differences in the RNA binding capacity of their respective RRMs.
对于几个组蛋白赖氨酸甲基转移酶（HKMTs），已经表明 RNA 结合是一个功能相关的特征，但这些蛋白质的 RNA 相互作用组的详细信息并不总是已知。在负责 H3K4 残基甲基化的六种人类 KMT2 蛋白中，有两个——SETD1A 和 SETD1B——包含 RNA 识别结构域（RRMs）。在这里，我们研究了 SETD1A 的 RNA 结合能力，并在 HEK293T 细胞中鉴定了广泛的相互作用 RNA。我们的分析表明，与酵母 Set1 相似，SETD1A 还能够结合多种编码和非编码 RNA，包括与 RNA 加工相关的 RNA 种类。我们还在体外显示了单个 RRM 结构域的直接 RNA 结合活性，这与酵母 Set1 中的 RRM 结构域形成对比。结构建模揭示了 SETD1A 可能的 RNA 识别模式的重要细节，并强调了 SETD1A 和 Set1 之间的一些基本差异，解释了它们各自的 RRMs 的 RNA 结合能力的差异。
