RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts

Jun Cao, Sunil K. Verma, Elizabeth Jaworski, Stephanie Mohan, Chloe K. Nagasawa, Kempaiah Rayavara, Amanda Sooter, Sierra N. Miller, Richard J. Holcomb, Mason J. Powell, Ping Ji, Nathan D. Elrod, Eda Yildirim, Eric J. Wagner, Vsevolod Popov, Nisha J. Garg, Andrew L. Routh, Muge N. Kuyumcu-Martinez

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 3ʹ-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.

Original languageEnglish (US)
Article number109910
JournalCell Reports
Volume37
Issue number5
DOIs
StatePublished - Nov 2 2021

Keywords

  • RBFOX2
  • Slc25a4
  • Tropomyosin 1
  • alternative polyadenylation
  • mitochondria
  • nanopore sequencing
  • poly(A) sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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