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Article: Endovascular treatment of intracranial aneurysms: Past and present.

Liang, Dongming

Journal of cerebrovascular and endovascular neurosurgery

2024

Abstract: Intracranial aneurysm is common in stroke and, once rupturing, will cause disaster to patients. Nowadays, endovascular treatment has become a routine to reduce the risk of intracranial aneurysms rupture. Successive endovascular methods, like balloon- ... ...

Abstract	Intracranial aneurysm is common in stroke and, once rupturing, will cause disaster to patients. Nowadays, endovascular treatment has become a routine to reduce the risk of intracranial aneurysms rupture. Successive endovascular methods, like balloon-assisted coiling, stent-assisted coiling, and flow diversion, have become new choices for doctors. More and more doctors have been entering this field. Understanding the current general situation is crucial for more medical workers to learn the endovascular treatment of intracranial aneurysms. In the past, many devices and ideas about the treatment of intracranial aneurysms appeared. Although developing unceasingly, endovascular treatment still has some deficiencies to overcome. The advantages and drawbacks of current endovascular methods are discussed.
Language	English
Publishing date	2024-01-19
Publishing country	Korea (South)
Document type	Journal Article
ISSN	2234-8565
ISSN	2234-8565
DOI	10.7461/jcen.2024.E2023.09.005
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Article ; Online: Expression and related mechanisms of miR-330-3p and S100B in an animal model of cartilage injury.

Wu, Wenming / Liang, Dongming

The Journal of international medical research

2021 Volume 49, Issue 9, Page(s) 3000605211039471

Abstract: Objective: To investigate the roles of and relationship between microRNA (miR)-330-3p and S100 calcium-binding protein B (S100B) in an animal model of cartilage injury.: Methods: This study included 30 New Zealand male rabbits randomly divided into ... ...

Abstract	Objective: To investigate the roles of and relationship between microRNA (miR)-330-3p and S100 calcium-binding protein B (S100B) in an animal model of cartilage injury. Methods: This study included 30 New Zealand male rabbits randomly divided into three groups: an intervention group, a model group and a sham surgery control group. Modelling was performed in the intervention and model groups, but in the sham surgery group, only the skin was cut. After modelling, the intervention and model groups were injected with the miR-330-3p overexpression vector GV268-miR-330-3p or the control GV268-N-ODN vector, respectively, twice a week for 7 weeks. Results: Levels of interleukin-1β and tumour necrosis factor-α in the synovial fluid were significantly higher in the model group than in the intervention and control groups. The level of miR-330-3p in the cartilage tissue was significantly higher in the control group than in the model group but it was significantly lower compared with the intervention group. Levels of S100B, fibroblast growth factor receptor 1 and fibroblast growth factor-2 in the cartilage tissue of rabbits in the model group were significantly higher compared with the control and intervention groups. Conclusion: These findings demonstrate that the upregulation of miR-330-3p can inhibit the expression of S100B.
MeSH term(s)	Animals ; Cartilage ; Cartilage Diseases ; Disease Models, Animal ; Male ; MicroRNAs/genetics ; Rabbits ; Synovial Fluid
Chemical Substances	MicroRNAs
Language	English
Publishing date	2021-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	184023-x
ISSN	1473-2300 ; 0300-0605 ; 0142-2596
ISSN (online)	1473-2300
ISSN	0300-0605 ; 0142-2596
DOI	10.1177/03000605211039471
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Article ; Online: CRISPR/Cas13 effectors have differing extents of off-target effects that limit their utility in eukaryotic cells.

Ai, Yuxi / Liang, Dongming / Wilusz, Jeremy E

Nucleic acids research

2022 Volume 50, Issue 11, Page(s) e65

Abstract: CRISPR/Cas13 effectors have garnered increasing attention as easily customizable tools for detecting and depleting RNAs of interest. Near perfect complementarity between a target RNA and the Cas13-associated guide RNA is required for activation of Cas13 ... ...

Abstract	CRISPR/Cas13 effectors have garnered increasing attention as easily customizable tools for detecting and depleting RNAs of interest. Near perfect complementarity between a target RNA and the Cas13-associated guide RNA is required for activation of Cas13 ribonuclease activity. Nonetheless, the specificity of Cas13 effectors in eukaryotic cells has been debated as the Cas13 nuclease domains can be exposed on the enzyme surface, providing the potential for promiscuous cleavage of nearby RNAs (so-called collateral damage). Here, using co-transfection assays in Drosophila and human cells, we found that the off-target effects of RxCas13d, a commonly used Cas13 effector, can be as strong as the level of on-target RNA knockdown. The extent of off-target effects is positively correlated with target RNA expression levels, and collateral damage can be observed even after reducing RxCas13d/guide RNA levels. The PspCas13b effector showed improved specificity and, unlike RxCas13d, can be used to deplete a Drosophila circular RNA without affecting the expression of the associated linear RNA. PspCas13b nonetheless still can have off-target effects and we notably found that the extent of off-target effects for Cas13 effectors differs depending on the cell type and target RNA examined. In total, these results highlight the need for caution when designing and interpreting Cas13-based knockdown experiments.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Drosophila/genetics ; Eukaryotic Cells ; RNA/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics
Chemical Substances	RNA, Guide, CRISPR-Cas Systems ; RNA (63231-63-0)
Language	English
Publishing date	2022-03-11
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac159
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Zs.A 1067: Show issues

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Article ; Online: Use of circular RNAs as markers of readthrough transcription to identify factors regulating cleavage/polyadenylation events.

Liang, Dongming / Tatomer, Deirdre C / Wilusz, Jeremy E

Methods (San Diego, Calif.)

2021 Volume 196, Page(s) 121–128

Abstract: Circular RNAs with covalently linked ends are generated from many eukaryotic protein-coding genes when the pre-mRNA splicing machinery backsplices. These mature transcripts are resistant to digestion by exonucleases and typically have much longer half- ... ...

Abstract	Circular RNAs with covalently linked ends are generated from many eukaryotic protein-coding genes when the pre-mRNA splicing machinery backsplices. These mature transcripts are resistant to digestion by exonucleases and typically have much longer half-lives than their associated linear mRNAs. Circular RNAs thus have great promise as sensitive biomarkers, including for detection of transcriptional activity. Here, we show that circular RNAs can serve as markers of readthrough transcription events in Drosophila and human cells, thereby revealing mechanistic insights into RNA polymerase II transcription termination as well as pre-mRNA 3' end processing. We describe methods that take advantage of plasmids that generate a circular RNA when an upstream polyadenylation signal fails to be used and/or RNA polymerase II fails to terminate. As a proof-of-principle, we show that RNAi-mediated depletion of well-established transcription termination factors, including the RNA endonuclease Cpsf73, results in increased circular RNA output from these plasmids in Drosophila and human cells. This method is generalizable as a circular RNA can be easily encoded downstream of any genomic region of interest. Circular RNA biomarkers, therefore, have great promise for identifying novel cellular factors and conditions that impact transcription termination processes.
MeSH term(s)	Biomarkers ; Polyadenylation/genetics ; RNA/genetics ; RNA/metabolism ; RNA Splicing/genetics ; RNA, Circular/genetics
Chemical Substances	Biomarkers ; RNA, Circular ; RNA (63231-63-0)
Language	English
Publishing date	2021-04-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2021.04.012
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Article: Use of circular RNAs as markers of readthrough transcription to identify factors regulating cleavage/polyadenylation events

Liang, Dongming / Tatomer, Deirdre C / Wilusz, Jeremy E

Methods. 2021 Apr. 15,

2021

Abstract	Circular RNAs with covalently linked ends are generated from many eukaryotic protein-coding genes when the pre-mRNA splicing machinery backsplices. These mature transcripts are resistant to digestion by exonucleases and typically have much longer half-lives than their associated linear mRNAs. Circular RNAs thus have great promise as sensitive biomarkers, including for detection of transcriptional activity. Here, we show that circular RNAs can serve as markers of readthrough transcription events in Drosophila and human cells, thereby revealing mechanistic insights into RNA polymerase II transcription termination as well as pre-mRNA 3′ end processing. We describe methods that take advantage of plasmids that generate a circular RNA when an upstream polyadenylation signal fails to be used and/or RNA polymerase II fails to terminate. As a proof-of-principle, we show that RNAi-mediated depletion of well-established transcription termination factors, including the RNA endonuclease Cpsf73, results in increased circular RNA output from these plasmids in Drosophila and human cells. This method is generalizable as a circular RNA can be easily encoded downstream of any genomic region of interest. Circular RNA biomarkers, therefore, have great promise for identifying novel cellular factors and conditions that impact transcription termination processes.
Keywords	DNA-directed RNA polymerase ; Drosophila ; biomarkers ; chemical bonding ; circular RNA ; digestion ; genomics ; half life ; humans ; plasmids ; transcription termination
Language	English
Dates of publication	2021-0415
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean ; Pre-press version
ZDB-ID	1066584-5
ISSN	1095-9130 ; 1046-2023
ISSN (online)	1095-9130
ISSN	1046-2023
DOI	10.1016/j.ymeth.2021.04.012
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Article ; Online: RNAi Screening to Identify Factors That Control Circular RNA Localization.

Tatomer, Deirdre C / Liang, Dongming / Wilusz, Jeremy E

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2209, Page(s) 321–332

Abstract: Thousands of eukaryotic protein-coding genes are noncanonically spliced to generate circular RNAs that have covalently linked ends. These transcripts are resistant to degradation by exonucleases, which enables some to accumulate to higher levels than the ...

Abstract	Thousands of eukaryotic protein-coding genes are noncanonically spliced to generate circular RNAs that have covalently linked ends. These transcripts are resistant to degradation by exonucleases, which enables some to accumulate to higher levels than the associated linear mRNA. In general, exonic circular RNAs accumulate in the cytoplasm, but functions for most of these transcripts remain unknown. It has been proposed that some may modulate the activity of microRNAs or RNA-binding proteins, be translated to yield protein products, or regulate innate immune responses. Recent work has revealed that circular RNAs are exported from the nucleus in a length-dependent manner and that the subcellular localization of these transcripts can be controlled by the DExH/D-box helicase Hel25E in Drosophila. Here, we describe how RNAi screening combined with subcellular fractionation and quantitative reverse transcription PCR (RT-qPCR) can be used to identify regulators of circular RNA localization in Drosophila cells. Long double-stranded RNAs (dsRNAs) that activate the RNA interference (RNAi) pathway are used to deplete factors of interest followed by biochemical fractionation to separate nuclear and cytoplasmic RNAs. RT-qPCR primers that amplify across the backsplicing junction of specific circular RNAs are then used to quantify the relative amounts of these transcripts in the nuclear and cytoplasmic compartments. In total, this approach can be broadly used to characterize circular RNA nuclear export and localization mechanisms, including to identify novel regulatory factors and their breadth of circular RNA targets.
MeSH term(s)	Active Transport, Cell Nucleus ; Animals ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; DEAD-box RNA Helicases/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/metabolism ; RNA Interference ; RNA Precursors/metabolism ; RNA Transport ; RNA, Circular/metabolism ; RNA, Double-Stranded/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	Drosophila Proteins ; RNA Precursors ; RNA, Circular ; RNA, Double-Stranded ; RNA-Binding Proteins ; Hel25E protein, Drosophila (EC 2.7.7.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2020-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0935-4_20
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Article ; Online: Short intronic repeat sequences facilitate circular RNA production.

Liang, Dongming / Wilusz, Jeremy E

Genes & development

2014 Volume 28, Issue 20, Page(s) 2233–2247

Abstract: Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. These RNAs are produced when the precursor messenger RNA (pre-mRNA) splicing machinery "backsplices" and covalently joins, for example, ...

Abstract	Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. These RNAs are produced when the precursor messenger RNA (pre-mRNA) splicing machinery "backsplices" and covalently joins, for example, the two ends of a single exon. However, the mechanism by which the spliceosome selects only certain exons to circularize is largely unknown. Using extensive mutagenesis of expression plasmids, we show that miniature introns containing the splice sites along with short (∼ 30- to 40-nucleotide) inverted repeats, such as Alu elements, are sufficient to allow the intervening exons to circularize in cells. The intronic repeats must base-pair to one another, thereby bringing the splice sites into close proximity to each other. More than simple thermodynamics is clearly at play, however, as not all repeats support circularization, and increasing the stability of the hairpin between the repeats can sometimes inhibit circular RNA biogenesis. The intronic repeats and exonic sequences must collaborate with one another, and a functional 3' end processing signal is required, suggesting that circularization may occur post-transcriptionally. These results suggest detailed and generalizable models that explain how the splicing machinery determines whether to produce a circular noncoding RNA or a linear mRNA.
MeSH term(s)	Base Pairing ; Base Sequence ; Humans ; Inteins/genetics ; Intracellular Signaling Peptides and Proteins/genetics ; Microsatellite Repeats/genetics ; Molecular Sequence Data ; Mutation ; Plasmids/genetics ; Protein-Serine-Threonine Kinases/genetics ; RNA/biosynthesis ; RNA/genetics ; RNA Splice Sites/genetics ; RNA, Circular ; Transcription Factors/genetics
Chemical Substances	Intracellular Signaling Peptides and Proteins ; RNA Splice Sites ; RNA, Circular ; Transcription Factors ; RNA (63231-63-0) ; HIPK3 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2014-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.251926.114
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Zs.A 2292: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Inducible Expression of Eukaryotic Circular RNAs from Plasmids.

Tatomer, Deirdre C / Liang, Dongming / Wilusz, Jeremy E

Methods in molecular biology (Clifton, N.J.)

2017 Volume 1648, Page(s) 143–154

Abstract: Thousands of eukaryotic protein-coding genes are noncanonically spliced to generate circular RNAs. Because they have covalently linked ends, circular RNAs are resistant to degradation by exonucleases and some accumulate to higher levels than their ... ...

Abstract	Thousands of eukaryotic protein-coding genes are noncanonically spliced to generate circular RNAs. Because they have covalently linked ends, circular RNAs are resistant to degradation by exonucleases and some accumulate to higher levels than their associated linear mRNAs. The functions of most circular RNAs are still unknown, but recent work has revealed key insights into how the pre-mRNA splicing machinery catalyzes backsplicing. Exons that circularize are often flanked by intronic repeat sequences that are complementary to one another, and backsplicing is triggered when these repeats base pair and bring the intervening splice sites into close proximity. Here, we describe how this knowledge has been translated into a simple plasmid-based method for ectopically expressing circular RNAs in eukaryotic cells. The sequence of interest is cloned into an artificial exon that is flanked by complementary intronic repeats. The plasmid is then transfected into cells, transcription is induced, and the cellular splicing machinery generates the desired circular RNA. Total RNA is isolated and the efficiency/specificity of circular RNA biogenesis is validated by Northern blot analysis. Beyond allowing overexpression of natural circular RNAs to define their functions, this approach can be used to produce designer RNA circles that are translated or bind specific cellular factors, such as microRNAs or proteins.
MeSH term(s)	Animals ; Cell Line ; Drosophila melanogaster ; Gene Expression ; Plasmids/genetics ; Plasmids/metabolism ; RNA Splicing ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-7204-3_11
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Article ; Online: IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.

Fujiwara, Rina / Zhai, Si-Nan / Liang, Dongming / Shah, Aayushi P / Tracey, Matthew / Ma, Xu-Kai / Fields, Christopher J / Mendoza-Figueroa, María Saraí / Meline, Michele C / Tatomer, Deirdre C / Yang, Li / Wilusz, Jeremy E

Molecular cell

2023 Volume 83, Issue 24, Page(s) 4445–4460.e7

Abstract: The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase ... ...

Abstract	The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset of Drosophila protein-coding genes, although having no effect on snRNAs or attenuation of other loci. Over-expressed IntS6 titrates protein phosphatase 2A (PP2A) subunits, thereby only affecting gene loci where phosphatase activity is necessary for Integrator function. IntS6 functions analogous to a PP2A regulatory B subunit as over-expression of canonical B subunits, which do not bind Integrator, is also sufficient to inhibit Integrator activity. These results show that the phosphatase module is critical at only a subset of Integrator-regulated genes and point to PP2A recruitment as a tunable step that modulates transcription termination efficiency.
MeSH term(s)	Animals ; RNA ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA, Small Nuclear/genetics ; Transcription Factors/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; Transcription Termination, Genetic
Chemical Substances	RNA (63231-63-0) ; RNA Polymerase II (EC 2.7.7.-) ; RNA, Small Nuclear ; Transcription Factors ; Drosophila Proteins
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/j.molcel.2023.10.035
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Zs.A 5055: Show issues

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Article ; Online: A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs.

Huang, Chuan / Liang, Dongming / Tatomer, Deirdre C / Wilusz, Jeremy E

Genes & development

2018 Volume 32, Issue 9-10, Page(s) 639–644

Abstract: Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of ... ...

Abstract	Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of the
MeSH term(s)	Active Transport, Cell Nucleus/genetics ; Amino Acid Sequence ; Amino Acids/genetics ; Animals ; Cell Line ; DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/metabolism ; Drosophila Proteins/genetics ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Evolution, Molecular ; Genetic Variation ; HeLa Cells ; Humans ; Protein Transport/genetics ; RNA/genetics ; RNA/metabolism ; RNA, Circular
Chemical Substances	Amino Acids ; Drosophila Proteins ; RNA, Circular ; RNA (63231-63-0) ; Hel25E protein, Drosophila (EC 2.7.7.-) ; DDX39A protein, human (EC 3.6.1.-) ; DDX39B protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2018-05-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.314856.118
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