A Circular RNA Binds To and Activates AKT Phosphorylation and Nuclear Localization Reducing Apoptosis and Enhancing Cardiac Repair

Zeng, Yan; Du, William W.; Wu, Yingya; Yang, Zhen-Guo; Awan, Faryal Mehwish; Li, Xiangmin; Yang, Weining; Zhang, Chao; Yang, Qi; Yee, Albert; Chen, Yu; Yang, Fenghua; Sun, Huan; Huang, Ren; Li, Ren‐Ke; Wu, Zhongkai; Backx, Peter H.; Yang, Burton B.

doi:10.7150/thno.19764

Cited by 328 publications

(283 citation statements)

References 43 publications

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“…The ecircRNA, circANRIL, was detected to function in the nucleus to modulate the ribosomal RNA maturation (Holdt et al, ). Another ecircRNA, circ‐Amotl1, can bind with PDK1 and AKT1, STAT3, and c‐myc and facilitate their nuclear translocation from cytoplasm and nucleus (Q. Zeng et al, ). In addition, intronic lariats can serve as a sort of “bait” for the TDP43 (TAR‐DNA binding protein 43) in the cytoplasm (Armakola et al, ).…”

Section: Functionmentioning

confidence: 99%

Intriguing circles: Conflicts and controversies in circular RNA research

2019

WIREs RNA

103

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Circular RNAs (circRNAs) are covalently closed RNA circles without a 5 0 cap or 3 0 tail. Since the landmark discovery of ciRS-7/CDR1as functioning as a miR-7 sponge in 2013, circRNAs have become a hot topic in RNA research. CircRNAs have been found to play active roles in cancer, cardiovascular diseases, neurological disorders, and many other diseases. They can function as microRNA (miRNA) sponges, protein scaffolds, and even translation templates. However, as circRNA research expands, many divergent views have emerged. For example, are most circRNAs competent in serving as miRNA sponges? What kinds of circRNAs are most likely to sponge miRNAs? Apart from sponging miRNAs, what could the functions of most circRNAs be? What are the features of circRNAs that are translatable? Many researchers have claimed that circRNAs are abundant, stable, conserved, and specific molecules, which hold great potential in serving as biomarkers. However, circRNA abundance is variable and some circRNAs are abundant while others are not. In addition, their stability and conservation may vary under different circumstances. Furthermore, it is unclear whether circRNA biogenesis is more likely to be regulated by RNA binding proteins or transcription factors. All of these are open questions that remain to be answered by researchers in this field. Discussing and investigating these questions will advance the understanding of this class of novel molecules and may propel inspiring new ideas for future studies.

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Section: Functionmentioning

confidence: 99%

Intriguing circles: Conflicts and controversies in circular RNA research

2019

WIREs RNA

103

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“…(c) CircAmotl1 suppress apoptosis events in cardiomyopathy-induced mouse models by facilitating the interaction between PDK1 kinase and its substrate AKT. Phosphorylated AKT originated from this scaffold-mediated interaction, is translocated to the nucleus and participates in the regulation of cell survival [43].…”

Section: Mirna Sponging By Circrnasmentioning

confidence: 99%

Circular RNA-Centered Regulatory Networks in the Physiopathology of Cardiovascular Diseases

Gabriel

Costa

Enguita

2020

IJMS

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Non-coding regulatory RNAs are generated as a core output of the eukaryotic genomes, being essential players in cell biology. At the organism level, they are key functional actors in those tissues and organs with limited proliferation capabilities such as the heart. The role of regulatory networks mediated by non-coding RNAs in the pathophysiology of cardiovascular conditions is starting to be unveiled. However, a deeper knowledge of the functional interactions among the diverse non-coding RNA families and their phenotypic consequences is required. This review presents the current knowledge about the functional crosstalk between circRNAs and other biomolecules in the framework of the cardiovascular diseases.

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“…In a circRNA‐microarray profiling comparing neonatal and mature postnatal human cardiac tissue samples, circAMOLT1 emerged as preferentially expressed in neonate hearts . circAMOLT1 physically binds to both PDK1 and AKT1, leading to AKT1 phosphorylation and nuclear translocation.…”

Section: Circrna In Cardiovascular Diseasesmentioning

confidence: 99%

“…3,13,14,36,48,49 A number of recent investigations take advantage Arraystar's microarrays and report strong detection and validation efficiency. [50][51][52][53][54][55][56] Microarray analysis removes the uncertainty that shrouds RNA-Seq analysis because of a lack of generalization. The procedure is targeted and, when the reproducibility and efficiency are ensured by the manufacturer, the standard analysis methods can be perfectly applied regardless of the hybridized RNA species.…”

Section: Micr Oar Raysmentioning

confidence: 99%

Circular RNAs: Methodological challenges and perspectives in cardiovascular diseases

Carrara

Fuschi

Ivan

et al. 2018

J Cellular Molecular Medi

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Circular RNAs are generated by back‐splicing of precursor‐mRNAs. Although they have been known for many years, only recently we have started to appreciate their widespread expression and their regulatory functions in a variety of biological processes. Not surprisingly, circular RNA dysregulation and participation in the pathogenic mechanisms have started to emerge in many instances, including cardiovascular diseases. Detection, differential expression analysis and validation are the three critical points for the characterization of any RNA, and circular RNAs are no exception. Their characteristics, however, generate several problems that are yet to be completely addressed, and literature still lacks comprehensive definitions of well‐defined best practices. We present a map of the current knowledge regarding circular RNAs and the critical issues limiting our understanding of their regulation and function. The goal was to provide the readers with the tools to critically decide which of the many approaches available is most suitable to their experimental plan. Although particularly focused on cardiovascular diseases, most critical issues concerning circular RNAs are common to many other fields of investigation.

show abstract

A Circular RNA Binds To and Activates AKT Phosphorylation and Nuclear Localization Reducing Apoptosis and Enhancing Cardiac Repair

Cited by 328 publications

References 43 publications

Intriguing circles: Conflicts and controversies in circular RNA research

Intriguing circles: Conflicts and controversies in circular RNA research

Circular RNA-Centered Regulatory Networks in the Physiopathology of Cardiovascular Diseases

Circular RNAs: Methodological challenges and perspectives in cardiovascular diseases

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