The expanding regulatory mechanisms and cellular functions of circular RNAs

Chen, Lingling

doi:10.1038/s41580-020-0243-y

Cited by 910 publications

(781 citation statements)

References 143 publications

Supporting

Mentioning

773

Contrasting

Order By: Relevance

“…It has recently been suggested that ciRS-7 could play a role in Alzheimer’s disease (AD) by targeting miRNA-7, which has been shown to play regulatory roles in the AD pathology [ 74 , 75 ]. Here, we focused on the direct production of Aβ peptides by circAβ isoforms, but we did not exclude possible indirect regulatory functions of circAβ isoforms such as regulation miRNA/mRNA interactions [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

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

Raabe

et al. 2020

Cells

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Raabe

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Our understanding of the human transcriptome has increased significantly by the discovery and understanding of the role of regulatory non-coding RNAs in physiology and diseases such as cancer (Vo et al, 2019). Among the non-coding regulatory transcripts, circRNAs have attracted intense research scrutiny in recent years (Chen, 2020). CircRNAs are single-stranded covalently closed continuous loop structures lacking free ends and a polyadenylate tail (Li X. et al, 2018b;Kristensen et al, 2019;Chen, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Among the non-coding regulatory transcripts, circRNAs have attracted intense research scrutiny in recent years (Chen, 2020). CircRNAs are single-stranded covalently closed continuous loop structures lacking free ends and a polyadenylate tail (Li X. et al, 2018b;Kristensen et al, 2019;Chen, 2020). Close to one-fifth of active genes in the human genome can potentially give rise to circRNAs (Salzman et al, 2012;Li X. et al, 2018b;Kristensen et al, 2019;Chen, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…CircRNAs are single-stranded covalently closed continuous loop structures lacking free ends and a polyadenylate tail (Li X. et al, 2018b;Kristensen et al, 2019;Chen, 2020). Close to one-fifth of active genes in the human genome can potentially give rise to circRNAs (Salzman et al, 2012;Li X. et al, 2018b;Kristensen et al, 2019;Chen, 2020). CircRNAs are composed of exonic and/or intronic sequences and are primarily generated by back-splicing, a non-canonical alternative RNA splicing event mediated by the spliceosome and regulated by a combination of cis-elements and trans-factors (Chen and Yang, 2015;Li X. et al, 2018b;Kristensen et al, 2019;Chen, 2020).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics

Rajappa

Banerjee

Sharma

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are rapidly coming to the fore as major regulators of gene expression and cellular functions. They elicit their influence via a plethora of diverse molecular mechanisms. It is not surprising that aberrant circRNA expression is common in cancers and they have been implicated in multiple aspects of cancer pathophysiology such as apoptosis, invasion, migration, and proliferation. We summarize the emerging role of circRNAs as biomarkers and therapeutic targets in cancer.

show abstract

“…Recent advances in RNA sequencing and bioinformatics tools have led to the discovery and identification of thousands of circRNAs and validated their important roles in the pathogenesis of cancers [ 18 , 19 , 20 , 21 ]. They can mainly function as ceRNAs to modulate gene transcription by interacting with miRNAs or lncRNAs, sponging miRNAs, or RNA-binding proteins, and rarely can be translated into proteins [ 22 , 23 , 24 , 25 ]. In addition to lncRNA and circRNA, other ceRNAs have also been identified by bioinformatics analysis and experimental evidence, such as pseudogenes, mRNA including those expressing 3′-untranslated regions, virus non-coding RNAs, and genomic viral RNAs [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

Zhang

Lü

2020

Cancers

View full text Add to dashboard Cite

Chemoresistance and metastasis are the main causes of treatment failure and unfavorable outcome in cancers. There is a pressing need to reveal their mechanisms and to discover novel therapy targets. Autophagy is composed of a cascade of steps controlled by different autophagy-related genes (ATGs). Accumulating evidence suggests that dysregulated autophagy contributes to chemoresistance and metastasis via competing endogenous RNA (ceRNA) networks including lncRNAs and circRNAs. ceRNAs sequester the targeted miRNA expression to indirectly upregulate ATGs expression, and thereof participate in autophagy-mediated chemoresistance and metastasis. Here, we attempt to summarize the roles of ceRNAs in cancer chemoresistance and metastasis through autophagy regulation.

show abstract

The expanding regulatory mechanisms and cellular functions of circular RNAs

Cited by 910 publications

References 143 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

Circular RNAs: Emerging Role in Cancer Diagnostics and Therapeutics

The Roles of ceRNAs-Mediated Autophagy in Cancer Chemoresistance and Metastasis

Contact Info

Product

Resources

About