RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts.
RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts.
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DOI：
10.1016/j.celrep.2021.109910
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发表时间：
2021-11-02
期刊：
影响因子：
8.8
通讯作者：
Kuyumcu-Martinez MN
中科院分区：
文献类型：
--
作者：
Cao J;Verma SK;Jaworski E;Mohan S;Nagasawa CK;Rayavara K;Sooter A;Miller SN;Holcomb RJ;Powell MJ;Ji P;Elrod ND;Yildirim E;Wagner EJ;Popov V;Garg NJ;Routh AL;Kuyumcu-Martinez MN
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. Cao et al. show that depletion of RBFOX2 in rat myoblasts modulates alternative polyadenylation patterns of mitochondrial and contractile genes. RBFOX2 loss adversely affects mitochondrial health.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
5.3
作者：
Cao J;Routh AL;Kuyumcu-Martinez MN
通讯作者：
Kuyumcu-Martinez MN
影响因子：
30.8
作者：
Liu X;Yagi H;Saeed S;Bais AS;Gabriel GC;Chen Z;Peterson KA;Li Y;Schwartz MC;Reynolds WT;Saydmohammed M;Gibbs B;Wu Y;Devine W;Chatterjee B;Klena NT;Kostka D;de Mesy Bentley KL;Ganapathiraju MK;Dexheimer P;Leatherbury L;Khalifa O;Bhagat A;Zahid M;Pu W;Watkins S;Grossfeld P;Murray SA;Porter GA Jr;Tsang M;Martin LJ;Benson DW;Aronow BJ;Lo CW
通讯作者：
Lo CW
影响因子：
5.8
作者：
Li, Heng
通讯作者：
Li, Heng
影响因子：
30.8
作者：
Graham, BH;Waymire, KG;Wallace, DC
通讯作者：
Wallace, DC