Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Nucleic Acids Res. 2020 Jun 4;48(10):5710-5719. doi: 10.1093/nar/gkaa295.
RNA binding proteins (RBPs) frequently regulate the expression of other RBPs in mammalian cells. Such cross-regulation has been proposed to be important to control networks of coordinated gene expression; however, much remains to be understood about how such networks of cross-regulation are established and what the functional consequence is of coordinated or reciprocal expression of RBPs. Here we demonstrate that the RBPs CELF2 and hnRNP C regulate the expression of each other, such that depletion of one results in reduced expression of the other. Specifically, we show that loss of hnRNP C reduces the transcription of CELF2 mRNA, while loss of CELF2 results in decreased efficiency of hnRNP C translation. We further demonstrate that this reciprocal regulation serves to fine tune the splicing patterns of many downstream target genes. Together, this work reveals new activities of hnRNP C and CELF2, provides insight into a previously unrecognized gene regulatory network, and demonstrates how cross-regulation of RBPs functions to shape the cellular transcriptome.
RNA 结合蛋白（RBPs）通常在哺乳动物细胞中调节其他 RBPs 的表达。这种交叉调节被认为对协调基因表达的控制网络很重要；然而，对于如何建立这种交叉调节网络以及协调或相互表达 RBPs 的功能后果，仍有许多需要了解。在这里，我们证明了 RBPs CELF2 和 hnRNP C 相互调节彼此的表达，以至于其中一种的缺失导致另一种的表达减少。具体来说，我们表明 hnRNP C 的缺失会降低 CELF2 mRNA 的转录，而 CELF2 的缺失会降低 hnRNP C 翻译的效率。我们进一步证明，这种相互调节有助于精细调整许多下游靶基因的剪接模式。总之，这项工作揭示了 hnRNP C 和 CELF2 的新活性，深入了解了一个以前未被识别的基因调控网络，并展示了 RBPs 的交叉调节如何作用于塑造细胞转录组。
