PDF(Pubmed)
Abstract：
RBFOX2, which has a well-established role in alternative splicing, is linked to heart diseases. However, it is unclear whether RBFOX2 has other roles in RNA processing that can influence gene expression in muscle cells, contributing to heart disease. Here, we employ both 3\'-end and nanopore cDNA sequencing to reveal a previously unrecognized role for RBFOX2 in maintaining alternative polyadenylation (APA) signatures in myoblasts. RBFOX2-mediated APA modulates mRNA levels and/or isoform expression of a collection of genes, including contractile and mitochondrial genes. Depletion of RBFOX2 adversely affects mitochondrial health in myoblasts, correlating with disrupted APA of mitochondrial gene Slc25a4. Mechanistically, RBFOX2 regulation of Slc25a4 APA is mediated through consensus RBFOX2 binding motifs near the distal polyadenylation site, enforcing the use of the proximal polyadenylation site. In sum, our results unveil a role for RBFOX2 in fine-tuning expression of mitochondrial and contractile genes via APA in myoblasts relevant to heart diseases.
摘要：
RBFOX2在可变剪接中具有公认的作用，与心脏病有关.然而,目前尚不清楚RBFOX2是否在RNA加工中具有其他作用，可以影响肌肉细胞中的基因表达，导致心脏病。这里,我们采用3'端和纳米孔cDNA测序来揭示RBFOX2在维持成肌细胞中的选择性聚腺苷酸化（APA）特征方面的作用。RBFOX2介导的APA调节基因集合的mRNA水平和/或同工型表达,包括收缩和线粒体基因.RBFOX2的耗尽对成肌细胞的线粒体健康产生不利影响，与线粒体基因Slc25a4的APA破坏相关。机械上,Slc25a4APA的RBFOX2调节是通过远端聚腺苷酸化位点附近的共有RBFOX2结合基序介导的，强制使用近端聚腺苷酸化位点。总之,我们的结果揭示了RBFOX2在通过APA微调与心脏病相关的成肌细胞中线粒体和收缩基因表达中的作用.
