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Article ; Online: Long non‐coding RNA OIP5‐AS1 (Cyrano)

Serena Wooten / Keriayn N. Smith

Clinical and Translational Medicine, Vol 12, Iss 1, Pp n/a-n/a (2022)

A context‐specific regulator of normal and disease processes

2022

Abstract: Abstract Long non‐coding (lnc) RNAs have been implicated in a plethora of normal biological functions, and have also emerged as key molecules in various disease processes. OIP5‐AS1, also commonly known by the alias Cyrano, is a lncRNA that displays broad ...

Abstract	Abstract Long non‐coding (lnc) RNAs have been implicated in a plethora of normal biological functions, and have also emerged as key molecules in various disease processes. OIP5‐AS1, also commonly known by the alias Cyrano, is a lncRNA that displays broad expression across multiple tissues, with significant enrichment in particular contexts including within the nervous system and skeletal muscle. Thus far, this multifaceted lncRNA has been found to have regulatory functions in normal cellular processes including cell proliferation and survival, as well as in the development and progression of a myriad disease states. These widespread effects on normal and disease states have been found to be mediated through context‐specific intermolecular interactions with dozens of miRNAs and proteins identified to date. This review explores recent studies to highlight OIP5‐AS1's contextual yet pleiotropic roles in normal homeostatic functions as well as disease oetiology and progression, which may influence its utility in the generation of future theranostics.
Keywords	cancer ; competing endogenous RNAs ; Cyrano ; diagnostic ; disease ; long non‐coding RNAs ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long non-coding RNA OIP5-AS1 (Cyrano): A context-specific regulator of normal and disease processes.

Wooten, Serena / Smith, Keriayn N

Clinical and translational medicine

2022 Volume 12, Issue 1, Page(s) e706

Abstract: Long non-coding (lnc) RNAs have been implicated in a plethora of normal biological functions, and have also emerged as key molecules in various disease processes. OIP5-AS1, also commonly known by the alias Cyrano, is a lncRNA that displays broad ... ...

Abstract	Long non-coding (lnc) RNAs have been implicated in a plethora of normal biological functions, and have also emerged as key molecules in various disease processes. OIP5-AS1, also commonly known by the alias Cyrano, is a lncRNA that displays broad expression across multiple tissues, with significant enrichment in particular contexts including within the nervous system and skeletal muscle. Thus far, this multifaceted lncRNA has been found to have regulatory functions in normal cellular processes including cell proliferation and survival, as well as in the development and progression of a myriad disease states. These widespread effects on normal and disease states have been found to be mediated through context-specific intermolecular interactions with dozens of miRNAs and proteins identified to date. This review explores recent studies to highlight OIP5-AS1's contextual yet pleiotropic roles in normal homeostatic functions as well as disease oetiology and progression, which may influence its utility in the generation of future theranostics.
MeSH term(s)	Disease/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics ; RNA, Long Noncoding/genetics
Chemical Substances	MicroRNAs ; RNA, Long Noncoding ; long noncoding RNA OIP5, human
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2697013-2
ISSN	2001-1326 ; 2001-1326
ISSN (online)	2001-1326
ISSN	2001-1326
DOI	10.1002/ctm2.706
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: RBBP4 dysfunction reshapes the genomic landscape of H3K27 methylation and acetylation and disrupts gene expression.

Mu, Weipeng / Murcia, Noel S / Smith, Keriayn N / Menon, Debashish U / Yee, Della / Magnuson, Terry

G3 (Bethesda, Md.)

2022 Volume 12, Issue 6

Abstract: RBBP4 is a subunit of the chromatin remodeling complexes known as Polycomb repressive complex 2 and histone deacetylase 1/2-containing complexes. These complexes are responsible for histone H3 lysine 27 methylation and deacetylation, respectively. How ... ...

Abstract	RBBP4 is a subunit of the chromatin remodeling complexes known as Polycomb repressive complex 2 and histone deacetylase 1/2-containing complexes. These complexes are responsible for histone H3 lysine 27 methylation and deacetylation, respectively. How RBBP4 modulates the functions of these complexes remains largely unknown. We generated viable Rbbp4 mutant alleles in mouse embryonic stem cell lines by CRISPR-Cas9. The mutations disrupted Polycomb repressive complex 2 assembly and H3K27me3 establishment on target chromatin and altered histone H3 lysine 27 acetylation genome wide. Moreover, Rbbp4 mutant cells underwent dramatic changes in transcriptional profiles closely tied to the deregulation of H3K27ac. The alteration of H3K27ac due to RBBP4 dysfunction occurred on numerous cis-regulatory elements, especially putative enhancers. These data suggest that RBBP4 plays a central role in regulating histone H3 lysine 27 methylation and acetylation to modulate gene expression.
MeSH term(s)	Acetylation ; Animals ; Gene Expression ; Genomics ; Histones/genetics ; Histones/metabolism ; Lysine/metabolism ; Methylation ; Mice ; Polycomb Repressive Complex 2/genetics ; Retinoblastoma-Binding Protein 4/metabolism
Chemical Substances	Histones ; Rbbp4 protein, mouse ; Retinoblastoma-Binding Protein 4 ; Polycomb Repressive Complex 2 (EC 2.1.1.43) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2022-04-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2629978-1
ISSN	2160-1836 ; 2160-1836
ISSN (online)	2160-1836
ISSN	2160-1836
DOI	10.1093/g3journal/jkac082
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Article ; Online: Interactome determination of a Long Noncoding RNA implicated in Embryonic Stem Cell Self-Renewal

Keriayn N. Smith / Joshua Starmer / Terry Magnuson

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 10

Abstract: Abstract Long noncoding RNAs (lncRNAs) constitute a significant fraction of mammalian transcriptomes and they have emerged as intricate regulators of many biological processes. Their broad capacity to adopt diverse structures facilitates their ... ...

Abstract	Abstract Long noncoding RNAs (lncRNAs) constitute a significant fraction of mammalian transcriptomes and they have emerged as intricate regulators of many biological processes. Their broad capacity to adopt diverse structures facilitates their involvement in the transcriptional, translational and signaling processes that are central to embryonic stem (ES) cell self-renewal and pluripotency. While lncRNAs have been implicated in ES cell maintenance, detailed analyses of those that show significant expression in ES cells is largely absent. Moreover, cooperative molecular relationships that facilitate lncRNA action are poorly understood. Cyrano is a developmentally important lncRNA, and in ES cells, it supports gene expression network maintenance, cell adhesion and cell survival. We have interrogated the interactome of Cyrano to identify protein partners and find that Cyrano is involved in multiple protein networks. We identify a developmentally important cell-signaling hub and find STAT3 as a candidate through which Cyrano can function to reinforce self-renewal of ES cells. Based on commonalities between ES cells and cancer cells, we postulate such functional interactions may support cell proliferation, cell identity and adhesion characteristics in rapidly proliferating cell types. The interactome data will therefore provide a resource for further investigations into interactions that regulate Cyrano or mediate its function.
Keywords	Medicine ; R ; Science ; Q
Subject code	612 ; 571
Language	English
Publishing date	2018-12-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Interactome determination of a Long Noncoding RNA implicated in Embryonic Stem Cell Self-Renewal.

Smith, Keriayn N / Starmer, Joshua / Magnuson, Terry

Scientific reports

2018 Volume 8, Issue 1, Page(s) 17568

Abstract: Long noncoding RNAs (lncRNAs) constitute a significant fraction of mammalian transcriptomes and they have emerged as intricate regulators of many biological processes. Their broad capacity to adopt diverse structures facilitates their involvement in the ... ...

Abstract	Long noncoding RNAs (lncRNAs) constitute a significant fraction of mammalian transcriptomes and they have emerged as intricate regulators of many biological processes. Their broad capacity to adopt diverse structures facilitates their involvement in the transcriptional, translational and signaling processes that are central to embryonic stem (ES) cell self-renewal and pluripotency. While lncRNAs have been implicated in ES cell maintenance, detailed analyses of those that show significant expression in ES cells is largely absent. Moreover, cooperative molecular relationships that facilitate lncRNA action are poorly understood. Cyrano is a developmentally important lncRNA, and in ES cells, it supports gene expression network maintenance, cell adhesion and cell survival. We have interrogated the interactome of Cyrano to identify protein partners and find that Cyrano is involved in multiple protein networks. We identify a developmentally important cell-signaling hub and find STAT3 as a candidate through which Cyrano can function to reinforce self-renewal of ES cells. Based on commonalities between ES cells and cancer cells, we postulate such functional interactions may support cell proliferation, cell identity and adhesion characteristics in rapidly proliferating cell types. The interactome data will therefore provide a resource for further investigations into interactions that regulate Cyrano or mediate its function.
MeSH term(s)	Animals ; Cell Adhesion/genetics ; Cell Differentiation/genetics ; Cell Proliferation/genetics ; Cell Self Renewal/genetics ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Gene Regulatory Networks ; Humans ; Mice ; STAT3 Transcription Factor/metabolism ; Signal Transduction/genetics ; Transcriptome/genetics
Chemical Substances	STAT3 Transcription Factor
Language	English
Publishing date	2018-12-04
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-34864-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multimodal Long Noncoding RNA Interaction Networks: Control Panels for Cell Fate Specification.

Smith, Keriayn N / Miller, Sarah C / Varani, Gabriele / Calabrese, J Mauro / Magnuson, Terry

Genetics

2019 Volume 213, Issue 4, Page(s) 1093–1110

Abstract: Lineage specification in early development is the basis for the exquisitely precise body plan of multicellular organisms. It is therefore critical to understand cell fate decisions in early development. Moreover, for regenerative medicine, the accurate ... ...

Abstract	Lineage specification in early development is the basis for the exquisitely precise body plan of multicellular organisms. It is therefore critical to understand cell fate decisions in early development. Moreover, for regenerative medicine, the accurate specification of cell types to replace damaged/diseased tissue is strongly dependent on identifying determinants of cell identity. Long noncoding RNAs (lncRNAs) have been shown to regulate cellular plasticity, including pluripotency establishment and maintenance, differentiation and development, yet broad phenotypic analysis and the mechanistic basis of their function remains lacking. As components of molecular condensates, lncRNAs interact with almost all classes of cellular biomolecules, including proteins, DNA, mRNAs, and microRNAs. With functions ranging from controlling alternative splicing of mRNAs, to providing scaffolding upon which chromatin modifiers are assembled, it is clear that at least a subset of lncRNAs are far from the transcriptional noise they were once deemed. This review highlights the diversity of lncRNA interactions in the context of cell fate specification, and provides examples of each type of interaction in relevant developmental contexts. Also highlighted are experimental and computational approaches to study lncRNAs.
MeSH term(s)	Cell Lineage/genetics ; Chromatin/metabolism ; Gene Regulatory Networks ; Humans ; Models, Biological ; Protein Stability ; RNA, Long Noncoding/chemistry ; RNA, Long Noncoding/genetics
Chemical Substances	Chromatin ; RNA, Long Noncoding
Language	English
Publishing date	2019-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2167-2
ISSN	1943-2631 ; 0016-6731
ISSN (online)	1943-2631
ISSN	0016-6731
DOI	10.1534/genetics.119.302661
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Article ; Online: Long Noncoding RNA Moderates MicroRNA Activity to Maintain Self-Renewal in Embryonic Stem Cells

Keriayn N. Smith / Joshua Starmer / Sarah C. Miller / Praveen Sethupathy / Terry Magnuson

Stem Cell Reports, Vol 9, Iss 1, Pp 108-

2017 Volume 121

Abstract: Of the thousands of long noncoding RNAs expressed in embryonic stem cells (ESCs), few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency, or the reprogramming of somatic cells to the ... ...

Abstract	Of the thousands of long noncoding RNAs expressed in embryonic stem cells (ESCs), few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency, or the reprogramming of somatic cells to the pluripotent state. In ESCs, Cyrano is a stably expressed long intergenic noncoding RNA with no previously assigned role. We demonstrate that Cyrano contributes to ESC maintenance, as its depletion results in the loss of hallmarks of self-renewal. Delineation of Cyrano's network through transcriptomics revealed widespread effects on signaling pathways and gene expression networks that contribute to ESC maintenance. Cyrano shares unique sequence complementarity with the differentiation-associated microRNA, mir-7, and mir-7 overexpression reduces expression of a key self-renewal factor to a similar extent as Cyrano knockdown. This suggests that Cyrano functions to restrain the action of mir-7. Altogether, we provide a view into the multifaceted function of Cyrano in ESC maintenance.
Keywords	Cyrano ; lncRNA ; embryonic stem cells ; self-renewal ; cell survival ; mir-7 ; nanog ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long Noncoding RNA Moderates MicroRNA Activity to Maintain Self-Renewal in Embryonic Stem Cells.

Smith, Keriayn N / Starmer, Joshua / Miller, Sarah C / Sethupathy, Praveen / Magnuson, Terry

Stem cell reports

2017 Volume 9, Issue 1, Page(s) 108–121

Abstract	Of the thousands of long noncoding RNAs expressed in embryonic stem cells (ESCs), few have known roles and fewer have been functionally implicated in the regulation of self-renewal and pluripotency, or the reprogramming of somatic cells to the pluripotent state. In ESCs, Cyrano is a stably expressed long intergenic noncoding RNA with no previously assigned role. We demonstrate that Cyrano contributes to ESC maintenance, as its depletion results in the loss of hallmarks of self-renewal. Delineation of Cyrano's network through transcriptomics revealed widespread effects on signaling pathways and gene expression networks that contribute to ESC maintenance. Cyrano shares unique sequence complementarity with the differentiation-associated microRNA, mir-7, and mir-7 overexpression reduces expression of a key self-renewal factor to a similar extent as Cyrano knockdown. This suggests that Cyrano functions to restrain the action of mir-7. Altogether, we provide a view into the multifaceted function of Cyrano in ESC maintenance.
Language	English
Publishing date	2017-07-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2017.05.005
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Article ; Online: Myc transcription factors: key regulators behind establishment and maintenance of pluripotency.

Smith, Keriayn / Dalton, Stephen

Regenerative medicine

2010 Volume 5, Issue 6, Page(s) 947–959

Abstract: The interplay between transcription factors, epigenetic modifiers, chromatin remodelers and miRNAs form the foundation of a complex regulatory network required for establishment and maintenance of the pluripotent state. Recent work indicates that Myc ... ...

Abstract	The interplay between transcription factors, epigenetic modifiers, chromatin remodelers and miRNAs form the foundation of a complex regulatory network required for establishment and maintenance of the pluripotent state. Recent work indicates that Myc transcription factors are essential elements of this regulatory system. However, despite numerous studies, aspects of how Myc controls self-renewal and pluripotency remain obscure. This article reviews evidence supporting the placement of Myc as a central regulator of the pluripotent state and discusses possible mechanisms of action.
MeSH term(s)	Animals ; Embryonic Development ; Humans ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/metabolism ; Proto-Oncogene Proteins c-myc/metabolism ; Stem Cell Transplantation ; Transcription Factors/metabolism
Chemical Substances	Proto-Oncogene Proteins c-myc ; Transcription Factors
Language	English
Publishing date	2010-11-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2274500-2
ISSN	1746-076X ; 1746-0751
ISSN (online)	1746-076X
ISSN	1746-0751
DOI	10.2217/rme.10.79
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Article ; Online: SWI/SNF remains localized to chromatin in the presence of SCHLAP1.

Raab, Jesse R / Smith, Keriayn N / Spear, Camarie C / Manner, Carl J / Calabrese, J Mauro / Magnuson, Terry

Nature genetics

2018 Volume 51, Issue 1, Page(s) 26–29

Abstract: SCHLAP1 is a long noncoding RNA that is reported to function by depleting the SWI/SNF complex from the genome. We investigated the hypothesis that SCHLAP1 affects only specific compositions of SWI/SNF. Using several assays, we found that SWI/SNF is not ... ...

Abstract	SCHLAP1 is a long noncoding RNA that is reported to function by depleting the SWI/SNF complex from the genome. We investigated the hypothesis that SCHLAP1 affects only specific compositions of SWI/SNF. Using several assays, we found that SWI/SNF is not depleted from the genome by SCHLAP1 and that SWI/SNF is associated with many coding and noncoding RNAs, suggesting that SCHLAP1 may function in a SWI/SNF-independent manner.
MeSH term(s)	Cell Line ; Chromatin/genetics ; Chromosomal Proteins, Non-Histone/genetics ; Genome, Human/genetics ; Humans ; RNA, Long Noncoding/genetics ; Transcription Factors/genetics
Chemical Substances	Chromatin ; Chromosomal Proteins, Non-Histone ; RNA, Long Noncoding ; SChLAP1 long noncoding RNA ; SWI-SNF-B chromatin-remodeling complex ; Transcription Factors
Language	English
Publishing date	2018-12-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-018-0272-z
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