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

Summary: 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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	RBFOX2 alternative polyadenylation mitochondria Slc25a4 Tropomyosin 1 nanopore sequencing Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1c3849ba190a44869afb25b4370a9f1a
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spelling	oai:doaj.org-article:1c3849ba190a44869afb25b4370a9f1a2021-11-04T04:28:55ZRBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts2211-124710.1016/j.celrep.2021.109910https://doaj.org/article/1c3849ba190a44869afb25b4370a9f1a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013838https://doaj.org/toc/2211-1247Summary: 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.Jun CaoSunil K. VermaElizabeth JaworskiStephanie MohanChloe K. NagasawaKempaiah RayavaraAmanda SooterSierra N. MillerRichard J. HolcombMason J. PowellPing JiNathan D. ElrodEda YildirimEric J. WagnerVsevolod PopovNisha J. GargAndrew L. RouthMuge N. Kuyumcu-MartinezElsevierarticleRBFOX2alternative polyadenylationmitochondriaSlc25a4Tropomyosin 1nanopore sequencingBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109910- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RBFOX2 alternative polyadenylation mitochondria Slc25a4 Tropomyosin 1 nanopore sequencing Biology (General) QH301-705.5
spellingShingle	RBFOX2 alternative polyadenylation mitochondria Slc25a4 Tropomyosin 1 nanopore sequencing Biology (General) QH301-705.5 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 RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
description	Summary: 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.
format	article
author	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
author_facet	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
author_sort	Jun Cao
title	RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
title_short	RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
title_full	RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
title_fullStr	RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
title_full_unstemmed	RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
title_sort	rbfox2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1c3849ba190a44869afb25b4370a9f1a
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RBFOX2 is critical for maintaining alternative polyadenylation patterns and mitochondrial health in rat myoblasts

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