Institute of Biochemistry, Justus Liebig University of Giessen, 35392 Giessen, Germany.
Nucleic Acids Res. 2020 Dec 2;48(21):12326-12335. doi: 10.1093/nar/gkaa1085.
Circular RNAs (circRNAs) are a class of noncoding RNAs, generated from pre-mRNAs by circular splicing of exons and functionally largely uncharacterized. Here we report on the design, expression, and characterization of artificial circRNAs that act as protein sponges, specifically binding and functionally inactivating hnRNP (heterogeneous nuclear ribonucleoprotein) L. HnRNP L regulates alternative splicing, depending on short CA-rich RNA elements. We demonstrate that designer hnRNP L-sponge circRNAs with CA-repeat or CA-rich sequence clusters can efficiently and specifically modulate splicing-regulatory networks in mammalian cells, including alternative splicing patterns and the cellular distribution of a splicing factor. This new strategy can in principle be applied to any RNA-binding protein, opening up new therapeutic strategies in molecular medicine.
环状 RNA（circRNAs）是一类非编码 RNA，通过外显子的环形剪接从前体 mRNA 产生，其功能很大程度上尚未确定。在这里，我们报告了人工环状 RNA 的设计、表达和特性，这些环状 RNA 可以作为蛋白质海绵，特异性结合和功能失活 hnRNP（异质核核糖核蛋白）L。hnRNP L 根据富含 CA 的短 RNA 元件调节选择性剪接。我们证明，具有 CA 重复或富含 CA 序列簇的设计 hnRNP L 海绵环状 RNA 可以在哺乳动物细胞中有效且特异性地调节剪接调控网络，包括选择性剪接模式和剪接因子的细胞分布。该新策略原则上可以应用于任何 RNA 结合蛋白，为分子医学开辟新的治疗策略。
