An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila

Weigelt, Carina Marianne; Sehgal, Rohan; Tain, Luke S; Cheng, Jianghua; Eßer, Jacqueline; Pahl, André; Dieterich, Christoph; Grönke, Sebastian; Partridge, Linda

doi:10.1016/j.molcel.2020.06.011

Cited by 95 publications

(87 citation statements)

References 73 publications

(117 reference statements)

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“…Albeit many, if not most, circular RNAs are probably neutral or slightly detrimental and non-functional by-products of hnRNA processing, a few might have detrimental effects for the organism by triggering cellular processes leading to disease; this might be the case for some of the circRNAs presented here. On the other hand, a few circRNAs, whether translated or not, might constitute an exaptation when the RNA or its translation product was co-opted into a variant or novel cellular function [ 85 , 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

Raabe

et al. 2020

Cells

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Alzheimer’s disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (Aβ) play a crucial role in the pathology of AD. In familial AD, Aβ are generated from the full-length amyloid beta precursor protein (APP) via dysregulated proteolytic processing; however, in the case of sporadic AD, the mechanism of Aβ biogenesis remains elusive. circRNAs are a class of transcripts preferentially expressed in brain. We identified a circRNA harboring the Aβ-coding region of the APP gene termed circAβ-a. This circular RNA was detected in the brains of AD patients and non-dementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circAβ-a is efficiently translated into a novel Aβ-containing Aβ175 polypeptide (19.2 KDa) in both cultured cells and human brain. Furthermore, Aβ175 was shown to be processed into Aβ peptides—a hallmark of AD. In summary, our analysis revealed an alternative pathway of Aβ biogenesis. Consequently, circAβ-a and its corresponding translation product could potentially represent novel therapeutic targets for AD treatment. Importantly, our data point to yet another evolutionary route for potentially increasing proteome complexity by generating additional polypeptide variants using back-splicing of primary transcripts that yield circular RNA templates.

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Section: Discussionmentioning

confidence: 99%

Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

Raabe

et al. 2020

Cells

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“…Recently, a study reported that circSfl was translated into a 25-kDa protein by sharing the N-terminus with the 110-kDa SFL protein encoded by host sulfateless ( sfl ) gene. Both proteins encoded by circSfl and linear SFL transcripts can regulate the life-span of flies, while the circSfl protein lacks the enzymatically active domain at the C terminus ( Weigelt et al, 2020 ).…”

Section: Formation and Function Of Circrnasmentioning

confidence: 99%

The role of circular RNAs in viral infection and related diseases

Xie

Sun

et al. 2021

Virus Research

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“…In 2020, Weigelt et al. (2020) showed that circSfl was highly upregulated in all tissues by next-generation sequencing of wild-type and mutant flies.…”

Section: Circrna Translation Potential: a Controversial Issue Explorementioning

confidence: 99%

“…Further study verified that circSfl is translated into a small protein that shares the N terminus with full-length Sfl protein. Furthermore, the protein encoded by circSfl and the protein encoded from the linear Sfl transcripts can positively extend the lifespan of female flies ( Weigelt et al., 2020 ), indicating the unique role of circSfl in fly life.…”

Section: Circrna Translation Potential: a Controversial Issue Explorementioning

confidence: 99%

Coding potential of circRNAs: new discoveries and challenges

Miao

Tang

2021

PeerJ

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The circular (circ)RNAs are a newly recognized group of noncoding (nc)RNAs. Research to characterize the functional features of circRNAs has uncovered distinctive profiles of conservation, stability, specificity and complexity. However, a new line of evidence has indicated that although circRNAs can function as ncRNAs, such as in the role of miRNA sponges, they are also capable of coding proteins. This discovery is no accident. In the last century, scientist detected the ability of translate in some virus and artificial circRNAs. Artificial circRNA translation products are usually nonfunctional, whereas natural circRNA translation products are completely different. Those new proteins have various functions, which greatly broadens the new ideas and research direction for our research. These series findings also raise questions about whether circRNA is still classified as non-coding RNA. Here, we summarize the evidence concerning translation potential of circRNAs, including synthetic and endogenous circRNA translation ability, and discuss the mechanisms of circRNA translation.

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An Insulin-Sensitive Circular RNA that Regulates Lifespan in Drosophila

Cited by 95 publications

References 73 publications

Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

Circular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease

The role of circular RNAs in viral infection and related diseases

Coding potential of circRNAs: new discoveries and challenges

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