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

Publication ,  Journal Article
Cao, J; Verma, SK; Jaworski, E; Mohan, S; Nagasawa, CK; Rayavara, K; Sooter, A; Miller, SN; Holcomb, RJ; Powell, MJ; Ji, P; Elrod, ND ...
Published in: Cell Rep
November 2, 2021

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 2, 2021

Volume

37

Issue

5

Start / End Page

109910

Location

United States

Related Subject Headings

  • Tropomyosin
  • Rats
  • RNA Splicing Factors
  • Polyadenylation
  • Myoblasts, Cardiac
  • Muscle Proteins
  • Mitochondrial Proteins
  • Mitochondria, Heart
  • Humans
  • HEK293 Cells
 

Citation

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Cao, J., Verma, S. K., Jaworski, E., Mohan, S., Nagasawa, C. K., Rayavara, K., … Kuyumcu-Martinez, M. N. (2021). RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts. Cell Rep, 37(5), 109910. https://doi.org/10.1016/j.celrep.2021.109910
Cao, Jun, Sunil K. Verma, Elizabeth Jaworski, Stephanie Mohan, Chloe K. Nagasawa, Kempaiah Rayavara, Amanda Sooter, et al. “RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts.Cell Rep 37, no. 5 (November 2, 2021): 109910. https://doi.org/10.1016/j.celrep.2021.109910.
Cao J, Verma SK, Jaworski E, Mohan S, Nagasawa CK, Rayavara K, et al. RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts. Cell Rep. 2021 Nov 2;37(5):109910.
Cao, Jun, et al. “RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts.Cell Rep, vol. 37, no. 5, Nov. 2021, p. 109910. Pubmed, doi:10.1016/j.celrep.2021.109910.
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 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts. Cell Rep. 2021 Nov 2;37(5):109910.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 2, 2021

Volume

37

Issue

5

Start / End Page

109910

Location

United States

Related Subject Headings

  • Tropomyosin
  • Rats
  • RNA Splicing Factors
  • Polyadenylation
  • Myoblasts, Cardiac
  • Muscle Proteins
  • Mitochondrial Proteins
  • Mitochondria, Heart
  • Humans
  • HEK293 Cells