Cell type-specific circular RNA expression in human glial cells

Curry‐Hyde, Ashton; Gray, Lachlan G.; Chen, Bei Jun; Ueberham, Uwe; Arendt, Thomas; Janitz, Michael

doi:10.1016/j.ygeno.2020.09.042

Cited by 16 publications

(9 citation statements)

References 51 publications

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“…Furthermore, recent studies concerning, for instance, the gut microbiota composition, have emphasized the ever-increasing role of peripheral inflammation in PD pathogenesis 92 . With respect to the circRNA transcriptomes of astrocytes and microglia, it was revealed that they are unique from one another and that the most abundant circRNAs are expressed by parent genes co-expressing linear RNAs in low abundance, indicating critical roles of circRNAs for glial function 93 .…”

Section: Circrnas In Pd Pathogenetic Processesmentioning

confidence: 99%

Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

Doxakis

2022

npj Parkinsons Dis.

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Parkinson’s disease (PD) is a complex, age-related, neurodegenerative disease whose etiology, pathology, and clinical manifestations remain incompletely understood. As a result, care focuses primarily on symptoms relief. Circular RNAs (circRNAs) are a large class of mostly noncoding RNAs that accumulate with aging in the brain and are increasingly shown to regulate all aspects of neuronal and glial development and function. They are generated by the spliceosome through the backsplicing of linear RNA. Although their biological role remains largely unknown, they have been shown to regulate transcription and splicing, act as decoys for microRNAs and RNA binding proteins, used as templates for translation, and serve as scaffolding platforms for signaling components. Considering that they are stable, diverse, and detectable in easily accessible biofluids, they are deemed promising biomarkers for diagnosing diseases. CircRNAs are differentially expressed in the brain of patients with PD, and growing evidence suggests that they regulate PD pathogenetic processes. Here, the biogenesis, expression, degradation, and detection of circRNAs, as well as their proposed functions, are reviewed. Thereafter, research linking circRNAs to PD-related processes, including aging, alpha-synuclein dysregulation, neuroinflammation, and oxidative stress is highlighted, followed by recent evidence for their use as prognostic and diagnostic biomarkers for PD.

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Section: Circrnas In Pd Pathogenetic Processesmentioning

confidence: 99%

Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

Doxakis

2022

npj Parkinsons Dis.

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“…In this study, we applied CARP to explore circRNA landscape and function in HOG cells and identified dynamic circRNA profiles during human OL development for the first time. A significant overlap of circRNA was found between HOG and OLs in the human post-mortem brain [ 19 ], demonstrating HOG as an in vitro system for human early OL development. In addition, much more circRNAs were identified from HOG cells, which represents an early OL progenitor cell stage, either showing better sensitivity of our method in detecting circRNA or a novel biology clue that there are much more circRNA expressed in the early OL stage, which may or may not be retained in mature OL stages.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the well-documented neuronal and synaptic circRNAs that display abnormalities in brain diseases [ 17 , 18 ], a comprehensive and precise understanding of the circRNA landscape and its downstream biological pathways in the human brain is still missing. Moreover, circRNAs were recently found in glia cells isolated from the post-mortem adult brains [ 19 ], including oligodendroglia (OL) that are responsible for myelinating neuronal axons to achieve rapid information flow in the brain [ 20 ]. Furthermore, alternative splicing is extensive in OLs that govern myelin development [ 21 ], and OL defects underlie neurodevelopmental and neurological diseases represented by schizophrenia and multiple sclerosis [ 22 – 24 ].…”

Section: Introductionmentioning

confidence: 99%

Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation

Teng

et al. 2022

Genome Biol

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Background Circular RNAs (circRNAs), a novel class of poorly conserved non-coding RNAs that regulate gene expression, are highly enriched in the human brain. Despite increasing discoveries of circRNA function in human neurons, the circRNA landscape and function in developing human oligodendroglia, the myelinating cells that govern neuronal conductance, remains unexplored. Meanwhile, improved experimental and computational tools for the accurate identification of circRNAs are needed. Results We adopt a published experimental approach for circRNA enrichment and develop CARP (CircRNA identification using A-tailing RNase R approach and Pseudo-reference alignment), a comprehensive 21-module computational framework for accurate circRNA identification and quantification. Using CARP, we identify developmentally programmed human oligodendroglia circRNA landscapes in the HOG oligodendroglioma cell line, distinct from neuronal circRNA landscapes. Numerous circRNAs display oligodendroglia-specific regulation upon differentiation, among which a subclass is regulated independently from their parental mRNAs. We find that circRNA flanking introns often contain cis-regulatory elements for RNA editing and are predicted to bind differentiation-regulated splicing factors. In addition, we discover novel oligodendroglia-specific circRNAs that are predicted to sponge microRNAs, which co-operatively promote oligodendroglia development. Furthermore, we identify circRNA clusters derived from differentiation-regulated alternative circularization events within the same gene, each containing a common circular exon, achieving additive sponging effects that promote human oligodendroglia differentiation. Conclusions Our results reveal dynamic regulation of human oligodendroglia circRNA landscapes during early differentiation and suggest critical roles of the circRNA-miRNA-mRNA axis in advancing human oligodendroglia development.

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“…Indeed, cell type differentiation and development are highly regulated processes mediated by circRNAs (Gapp et al, 2014 ; Meng et al, 2019 ). Recent investigations have shown that circRNAs regulate neuronal and glial lineages (astrocytes, oligodendrocytes, and microglia) by functioning as gene transcription regulators (Curry-Hyde et al, 2020 ; Salvatori et al, 2020 ; Suster and Feng, 2021 ). Another role of the circRNAs has been reported during development of the neocortex where they regulate spontaneous neuronal differentiation and are important to maintain the pool of cell progenitors (Suenkel et al, 2020 ).…”

Section: Circrnas In Cnsmentioning

confidence: 99%

Circular RNAs: The Novel Actors in Pathophysiology of Spinal Cord Injury

Sámano

Mladinić

Mazzone

2021

Front. Integr. Neurosci.

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Spinal Cord Injury (SCI) can elicit a progressive loss of nerve cells promoting disability, morbidity, and even mortality. Despite different triggering mechanisms, a cascade of molecular events involving complex gene alterations and activation of the neuroimmune system influence either cell damage or repair. Effective therapies to avoid secondary mechanisms underlying SCI are still lacking. The recent progression in circular RNAs (circRNAs) research has drawn increasing attention and opened a new insight on SCI pathology. circRNAs differ from traditional linear RNAs and have emerged as the active elements to regulate gene expression as well as to facilitate the immune response involved in pathophysiology-related conditions. In this review, we focus on the impact and possible close relationship of circRNAs with pathophysiological mechanisms following SCI, where circRNAs could be the key transcriptional regulatory molecules to define neuronal death or survival. Advances in circRNAs research provide new insight on potential biomarkers and effective therapeutic targets for SCI patients.

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Cell type-specific circular RNA expression in human glial cells

Cited by 16 publications

References 51 publications

Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

Insights into the multifaceted role of circular RNAs: implications for Parkinson’s disease pathogenesis and diagnosis

Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation

Circular RNAs: The Novel Actors in Pathophysiology of Spinal Cord Injury

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