Faculty of Medicine, University of Cologne, Cluster of Excellence on Cellular Stress Responses in Aging-associated Diseases (CECAD), University Hospital of Cologne, Köln, Germany.
Institute of Virology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
RNA Biol. 2024 Jan;21(1):1-13. doi: 10.1080/15476286.2024.2413820. Epub 2024 Oct 10.
(RNA-binding motif protein 3) is a stress responsive gene, which maintains cellular homeostasis and promotes survival upon various harmful cellular stimuli. Rbm3 protein shows conserved structural and molecular similarities to heterogeneous nuclear ribonucleoproteins (hnRNPs), which regulate all steps of the mRNA metabolism. Growing evidence is pointing towards a broader role of Rbm3 in various steps of gene expression. Here, we demonstrate that Rbm3 deficiency is linked to transcriptome-wide pre-mRNA splicing alterations, which can be reversed through Rbm3 co-expression from a cDNA. Using an MS2 tethering assay, we show that Rbm3 regulates splice site selection similar to other hnRNP proteins when recruited between two competing 5 splice sites. Furthermore, we show that the N-terminal part of Rbm3 encompassing the RNA recognition motif (RRM), is sufficient to elicit changes in splice site selection. On the basis of these findings, we propose a novel, undescribed function of Rbm3 in RNA splicing that contributes to the preservation of transcriptome integrity.
（RNA 结合基序蛋白 3）是一种应激反应基因，它维持细胞内稳态，并在各种有害细胞刺激下促进存活。Rbm3 蛋白与异质核核糖核蛋白（hnRNPs）表现出保守的结构和分子相似性，hnRNPs 调节 mRNA 代谢的所有步骤。越来越多的证据表明，Rbm3 在基因表达的各个步骤中具有更广泛的作用。在这里，我们证明 Rbm3 缺乏与全转录组 pre-mRNA 剪接改变有关，这些改变可以通过 cDNA 共表达 Rbm3 来逆转。使用 MS2 tethering assay，我们表明当 Rbm3 被募集到两个竞争的 5 剪接位点之间时，它类似于其他 hnRNP 蛋白调节剪接位点选择。此外，我们表明 Rbm3 的 N 端包含 RNA 识别基序（RRM），足以引起剪接位点选择的变化。基于这些发现，我们提出了 Rbm3 在 RNA 剪接中的一种新的、未被描述的功能，它有助于保持转录组的完整性。
