p38α MAPK proximity assay reveals a regulatory mechanism of alternative splicing in cardiomyocytes

Dumont, Audrey-Ann; Dumont, L; Berthiaume, Jonathan; Auger‐Messier, Mannix

doi:10.1016/j.bbamcr.2019.118557

Cited by 16 publications

(15 citation statements)

References 77 publications

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“…The first article described several unstable mRNAs involved in cardiac contraction due to a lack of 5' capping in Srsf3 conditional knockout (cKO) mice through an Srsf3-mTOR-eIF4E mechanism (Ortiz-Sanchez et al, 2019). The second study revealed the capacity of p38 MAPK to modulate the splicing activity of Srsf3 in cultured primary neonatal rat ventricular myocytes (Dumont et al, 2019).…”

Section: Introductionmentioning

confidence: 97%

Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role

Dumont

Zhou

et al. 2020

Preprint

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AbstractSrsf3 was recently reported as being necessary to preserve RNA stability via an mTOR mechanism in a cardiac mouse model in adulthood. Here, we demonstrate the link between Srsf3 and mitochondrial integrity in an embryonic cardiomyocyte-specific Srsf3 conditional knockout (cKO) mouse model. Fifteen-day-old Srsf3 cKO mice showed dramatically reduced (below 50%) survival and reduced left ventricular systolic performance, and histological analysis of these hearts revealed a significant increase in cardiomyocyte size, confirming the severe remodelling induced by Srsf3 deletion. RNA-seq analysis of the hearts of 5-day-old Srsf3 cKO mice revealed early changes in expression levels and alternative splicing of several transcripts related to mitochondrial integrity and oxidative phosphorylation. Likewise, the levels of several protein complexes of the electron transport chain decreased, and mitochondrial complex I-driven respiration of permeabilized cardiac muscle fibres from the left ventricle was impaired. Furthermore, transmission electron microscopy analysis showed disordered mitochondrial length and cristae structure. Together with its indispensable role in the physiological maintenance of mouse hearts, these results highlight the previously unrecognized function of Srsf3 in regulating mitochondrial integrity.

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Section: Introductionmentioning

confidence: 97%

Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role

Dumont

Zhou

et al. 2020

Preprint

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“…For example, the mitogen-activated protein kinase (MAPK) signaling pathway is often dynamically involved in various physiological processes under different stress conditions, and it is difficult for traditional methods to simultaneously capture MAPK substrates in different states. Dumont et al. (2019) used APEX2-based PL to map the interactome of p38α and p38γ MAPKs under both steady-state and activated conditions and identified novel substrates of p38.…”

Section: Introductionmentioning

confidence: 99%

Proximity labeling: an emerging tool for probing in planta molecular interactions

Yang

Wen

Zhang

et al. 2021

Plant Communications

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Protein–protein interaction (PPI) networks are key to nearly all aspects of cellular activity. Therefore, the identification of PPIs is important for understanding a specific biological process in an organism. Compared with conventional methods for probing PPIs, the recently described proximity labeling (PL) approach combined with mass spectrometry (MS)-based quantitative proteomics has emerged as a powerful approach for characterizing PPIs. However, the application of PL in planta remains in its infancy. Here, we summarize recent progress in PL and its potential utilization in plant biology. We specifically summarize advances in PL, including the development and comparison of different PL enzymes and the application of PL for deciphering various molecular interactions in different organisms with an emphasis on plant systems.

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“…14 The second study revealed the capacity of p38 MAPK to modulate the splicing activity of Srsf3 in cultured primary neonatal rat ventricular myocytes. 15 Abnormal RNA splicing is an important contributor to the development of cardiomyopathies. [16][17][18][19][20] In fact, many studies have been performed to understand the impact of distinct splicing factors on mRNA expression and splicing from a cardiac perspective via the use of human heart samples and cardiac mouse models.…”

Section: Introductionmentioning

confidence: 99%

“…The first article described several unstable mRNAs involved in cardiac contraction due to a lack of 5’ capping in Srsf3 conditional knockout (cKO) mice through an Srsf3‐mTOR‐eIF4E mechanism 14 . The second study revealed the capacity of p38 MAPK to modulate the splicing activity of Srsf3 in cultured primary neonatal rat ventricular myocytes 15 …”

Section: Introductionmentioning

confidence: 99%

Cardiomyocyte‐specific Srsf3 deletion reveals a mitochondrial regulatory role

Dumont

Zhou

et al. 2021

FASEB j.

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Serine-rich splicing factor 3 (SRSF3) was recently reported as being necessary to preserve RNA stability via an mTOR mechanism in a cardiac mouse model in adulthood. Here, we demonstrate the link between Srsf3 and mitochondrial integrity in an embryonic cardiomyocyte-specific Srsf3 conditional knockout (cKO) mouse model.Fifteen-day-old Srsf3 cKO mice showed dramatically reduced (below 50%) survival and reduced the left ventricular systolic performance, and histological analysis of these hearts revealed a significant increase in cardiomyocyte size, confirming the severe remodeling induced by Srsf3 deletion. RNA-seq analysis of the hearts of 5-day-old Srsf3 cKO mice revealed early changes in expression levels and alternative splicing of several transcripts related to mitochondrial integrity and oxidative phosphorylation. Likewise, the levels of several protein complexes of the electron transport chain decreased, and mitochondrial complex I-driven respiration of permeabilized cardiac muscle fibers from the left ventricle was impaired. Furthermore, transmission electron microscopy analysis showed disordered mitochondrial length and cristae structure. Together with its indispensable role in the physiological maintenance of mouse hearts, these results highlight the previously unrecognized function of Srsf3 in regulating the mitochondrial integrity. K E Y W O R D S cardiomyocyte, mitochondria, oxidative phosphorylation, respiratory chain complex I, Srsf3 2 of 18 | DUMONT eT al.

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p38α MAPK proximity assay reveals a regulatory mechanism of alternative splicing in cardiomyocytes

Cited by 16 publications

References 77 publications

Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role

Cardiomyocyte-specific Srsf3 deletion reveals a mitochondrial regulatory role

Proximity labeling: an emerging tool for probing in planta molecular interactions

Cardiomyocyte‐specific Srsf3 deletion reveals a mitochondrial regulatory role

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