Parentally inherited long non-coding RNA Cyrano is involved in zebrafish neurodevelopment

Sarangdhar, Mayuresh Anant; Chaubey, Divya; Srikakulam, Nagesh; Pillai, Beena

doi:10.1093/nar/gky628

Cited by 37 publications

(26 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mode of transportation of RNAs may be via membrane-bound vesicles that are expelled from cells and contain an abundance of small RNAs [15][16][17], including miRNAs [18]. Long non-coding RNAs have also been indirectly postulated to be transferred to offspring due to experience-dependent alterations in the sperm [19][20][21][22]. We, therefore, postulated that somatically expressed RNAs may be transported to the germline allowing real-time heritability of somatic, experience-dependent alterations.…”

Section: Introductionmentioning

confidence: 99%

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

O’Brien

Ensbey

Day

et al. 2019

Preprint

View full text Add to dashboard Cite

AbstractBackgroundThe traditional concept that heritability occurs exclusively from the transfer of germline-restricted genetics is being challenged by the increasing accumulation of evidence confirming the existence of experience-dependent transgenerational inheritance. However, questions remain unanswered as to how heritable information can be passed from somatic cells. Previous studies have implicated the critical involvement of RNA in heritable transgenerational effects and the high degree of mobility and genomic impact of RNAs in all organisms is an attractive model for the efficient transfer of genetic information.ResultsWe hypothesized that RNA may be transported from a somatic tissue, in this case the brain, of an adult male mouse to the germline, and subsequently to offspring. To investigate this, we injected one hemisphere of the male mouse striatum with an AAV1/9 virus expressing human pre-MIR941 (MIR941). After 2, 8 and 16 weeks following injection, we used an LNA-based qPCR system to detect the presence of virus and human MIR941 in brain, peripheral tissues and offspring, from injected male mice mated with uninjected females. Virus was never detected outside of the brain. Verification of single bands of the correct size for MIR941 was performed using Sanger sequencing while quantitation demonstrated that a small percentage (∼ 1-8%) of MIR941 is transported to the germline and to offspring in about a third of the cases.ConclusionsWe show that somatic RNA can be transported to the germline and passed on to offspring, thereby providing additional evidence of a role for RNA in somatic cell-derived transgenerational effects.

show abstract

Section: Introductionmentioning

confidence: 99%

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

O’Brien

Ensbey

Day

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…The third column shows the transcript ID for the investigated lncRNA or its genomic coordinate in GRCz10. Column Four represents the expression dynamics of the lncRNAs (see also Figure S3) (log2 (FPKM +1) between 0 and 8) 25 Cyrano cyrano is evolutionarily conserved lncRNA and based on morpholino studies, has been suggested to have essential functions during zebrafish embryogenesis 23 and brain morphogenesis 32 . cyrano has also been suggested to act as a sponge (decoy-factor) for HuR during neuronal proliferation 33 , regulate miR-7 mediated embryonic stem cell differentiation 34 , and control the level of miR-7 in the adult mouse brain 35 .…”

mentioning

confidence: 99%

Long non-coding RNAs are largely dispensable for zebrafish embryogenesis, viability and fertility

Goudarzi

Berg

Pieper

et al. 2018

Preprint

View full text Add to dashboard Cite

Hundreds of long non-coding RNAs (lncRNAs) have been identified as potential regulators of gene expression, but their functions remain largely unknown. To study the role of lncRNAs during vertebrate development, we selected 25 zebrafish lncRNAs based on their conservation, expression profile or proximity to developmental regulators, and used CRISPR-Cas9 to generate 32 deletion alleles. We observed altered transcription of neighboring genes in some mutants, but none of the lncRNAs were required for embryogenesis, viability or fertility. Even RNAs with previously proposed non-coding functions (cyrano and squint) and other conserved lncRNAs (gas5 and lnc-setd1ba) were dispensable. In one case (lnc-phox2bb), absence of putative DNA regulatory-elements, but not of the lncRNA transcript itself, resulted in abnormal development. LncRNAs might have redundant, subtle, or context-dependent roles, but extrapolation from our results suggests that the majority of individual zebrafish lncRNAs are dispensable for embryogenesis, viability and fertility.

show abstract

“…The lncRNA OIP5-AS1 (known as Cyrano in zebrafish) is highly and ubiquitously expressed in various tissues and species 12 . 12 Cyrano has been shown to promoting zebrafish brain development, and silencing of Cyrano by miR-7 without changing zygotic Cyrano altered the brain architecture at 24 hours post fertilization and 48 hours post fertilization 13 . 13 In the lens, OIP5-AS1 is upregulated in the HLECs of patients with cataracts.…”

mentioning

confidence: 99%

“… 12 Cyrano has been shown to promoting zebrafish brain development, and silencing of Cyrano by miR-7 without changing zygotic Cyrano altered the brain architecture at 24 hours post fertilization and 48 hours post fertilization 13 . 13 In the lens, OIP5-AS1 is upregulated in the HLECs of patients with cataracts. 10 This molecule has been reported as a tumor suppressor or oncogene depending on the tumor type.…”

mentioning

confidence: 99%

Long Noncoding RNA OIP5-AS1 Promotes Cell Apoptosis and Cataract Formation by Blocking POLG Expression Under Oxidative Stress

Jing

et al. 2020

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Cataract, a clouding of the intraocular lens, is the leading cause of blindness. The lens-expressed long noncoding RNA OIP5-AS1 was upregulated in lens epithelial cells from patients with cataracts, suggesting its pathogenic role in cataracts. We investigated the regulatory role of OIP5-AS1 in the development of cataracts as well as potential RNA binding proteins, downstream target genes, and upstream transcription factors. Methods Clinical capsules and ex vivo and in vitro cataract models were used to test OIP5-AS1 expression. Cell apoptosis was detected using Western blots, JC-1 staining, and flow cytometry. Ribonucleoprotein immunoprecipitation-qPCR was performed to confirm the interaction of OIP5-AS1 and POLG . Chromatin immunoprecipitation-qPCR was used to determine the binding of TFAP2A and the OIP5-AS1 promoter region. Results OIP5-AS1 was upregulated in cataract lenses and B3 cells under oxidative stress. OIP5-AS1 knockdown protected B3 cells from H 2 O 2 -induced apoptosis and alleviated lens opacity in the ex vivo cataract model. HuR functioned as a scaffold carrying OIP5-AS1 and POLG mRNA and mediated the decay of POLG mRNA. POLG was downregulated in the cataract lens and oxidative-stressed B3 cells, and POLG depletion decreased the mtDNA copy number and MMP, increased reactive oxygen species production, and sensitized B3 cells to oxidative stress-induced apoptosis. POLG overexpression reversed these effects. TFAP2A bound the OIP5-AS1 promoter and contributed to OIP5-AS1 expression. Conclusions We demonstrated that OIP5-AS1 , activated by TFAP2A , contributed to cataract formation by inhibiting POLG expression mediated by HuR, thus leading to increased apoptosis of lens epithelial cells and aggravated lens opacity, suggesting that OIP5-AS1 is a potential target for cataract treatment.

show abstract

Parentally inherited long non-coding RNA Cyrano is involved in zebrafish neurodevelopment

Cited by 37 publications

References 28 publications

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

Long non-coding RNAs are largely dispensable for zebrafish embryogenesis, viability and fertility

Long Noncoding RNA OIP5-AS1 Promotes Cell Apoptosis and Cataract Formation by Blocking POLG Expression Under Oxidative Stress

Contact Info

Product

Resources

About