RISC RNA Sequencing for Context-Specific Identification of In Vivo MicroRNA Targets

Abnormal mitochondrial fission participates in the pathogenesis of many diseases. Long non-coding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the regulation of mitochondrial network is unclear. Here we report that a lncRNA, named cardiac apoptosis-related lncRNA (CARL), can suppress mitochondrial fission and apoptosis by targeting miR-539 and PHB2. The results show that PHB2 is able to inhibit mitochondrial fission and apoptosis. miR-539 is responsible for the dysfunction of PHB2 and regulates mitochondrial fission and apoptosis by targeting PHB2. Further, we show that CARL can act as an endogenous miR-539 sponge that regulates PHB2 expression, mitochondrial fission and apoptosis. Our present study reveals a model of mitochondrial fission regulation that is composed of CARL, miR-539 and PHB2. Modulation of their levels may provide a new approach for tackling apoptosis and myocardial infarction.

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“…miRNAs have been reported to regulate apoptosis in cardiomyocytes [33][34][35] . More than 800 miRNAs have been identified.…”

Section: Discussionmentioning

confidence: 99%

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

et al. 2014

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“…Some miRNAs have been reported to regulate apoptosis in cardiomyocytes 6,41,42 . However, few works have been focused on miRNAs in the mitochondrial network regulation.…”

Section: Pink1 Inhibits Mitochondrial Fragmentation and Apoptosismentioning

confidence: 99%

E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1

Wang

Zhou

et al. 2015

Nat Commun

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Mitochondrial fragmentation plays an important role in the progression of cardiac diseases, such as myocardial infarction and heart failure. Mitochondrial network is controlled by many factors in different cell types. Here we show that the interplay between E2F1, miR-421 and Pink1 regulates mitochondrial morphology and cardiomyocyte cell death. Pink1 reduces mitochondrial fragmentation and protects cardiomyocyte from apoptosis. On the other hand, miR-421 promotes cardiomyocyte mitochondrial fragmentation, apoptosis and myocardial infarction by suppressing Pink1 translation. Finally, we show that transcription factor E2F1 activates miR-421 expression. Knocking down E2F1 suppresses mitochondrial fragmentation, apoptosis and myocardial infarction by affecting miR-421 levels. Collectively, these data identify the E2F1/miR-421/Pink axis as a regulator of mitochondrial fragmentation and cardiomyocyte apoptosis, and suggest potential therapeutic targets in treatment of cardiac diseases.

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“…MicroRNAs (miRNAs) 3 are 21-23-nucleotide singlestranded noncoding RNA molecules that are found to be gene expression regulators and can affect mRNA stability or translation efficiency (1)(2)(3). Growing evidence has revealed that miRNAs are involved in the control of the hypertrophic program (4 -9).…”

mentioning

confidence: 99%

Cardiac Hypertrophy Is Positively Regulated by MicroRNA miR-23a

Wang

Lin

Long

et al. 2012

Journal of Biological Chemistry

102

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RISC RNA Sequencing for Context-Specific Identification of In Vivo MicroRNA Targets

Cited by 102 publications

References 34 publications

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

CARL lncRNA inhibits anoxia-induced mitochondrial fission and apoptosis in cardiomyocytes by impairing miR-539-dependent PHB2 downregulation

E2F1-dependent miR-421 regulates mitochondrial fragmentation and myocardial infarction by targeting Pink1

Cardiac Hypertrophy Is Positively Regulated by MicroRNA miR-23a

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