Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans

Nepal, Chirag; Taranta, Andrzej; Hadzhiev, Yavor; Pundhir, Sachin; Mydel, Piotr; Lenhard, Boris; Müller, Ferenc; Andersen, Jesper B.

doi:10.1016/j.isci.2020.101008

Cited by 13 publications

(21 citation statements)

References 59 publications

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“…More than 1000 of these non-coding RNAs are persistently conserved from generation to generation [22]. Lately, the conserved DNA non-coding elements (CNE) and their long noncoding RNAs (lncRNA) have been intensively studied by many groups with the help of sophisticated numerical analysis methods [23,24]. Their findings are impressive.…”

Section: A)the Traditional Approachmentioning

confidence: 99%

“…The CNEs play different roles in normal development and disease coordinating spatial-temporal gene expression in both embryos and grown up animals. A CNE that has been thoroughly studied is Hotair which is a lncRNA located between HOXC11 and HOXC12 in the vertebrate chromosome 12 [24]. In the early studies of CNEs it was reported the striking differences in structure and function of the CNEs occur for various vertebrates, in particular in Humans and mice [25].…”

Section: A)the Traditional Approachmentioning

confidence: 99%

“…In view of the above findings, an International Bioinformatics Group in collaboration with the with HOXC11 in cis and negatively correlated with HOXD11 in trans [24]. They compared human and zebrafish CNEs and identified a 32-nucleotide long CNE conserved across the vertebrates.…”

Section: A)the Traditional Approachmentioning

confidence: 99%

“…They characterized this long CNE as the ancestral sequence of the ancestral HoxC/D cluster . Their conclusion is that a lncRNA locus functions at the DNA and RNA levels regulating genes both in cis and in trans [24] .This is a challenging hypothesis to be further tested. More specifically, this analysis indicates that HOTAIR expression regulates positively human HOXC11 in cis and negatively HOXD11 in trans [24].The number of the conserved elements varies, depending on the cluster copies during the whole genome duplications.…”

Section: A)the Traditional Approachmentioning

confidence: 99%

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Recent Experiments Raised Doubt On the Vertebrate Temporal Collinearity of the Hox Genes. A Biophysical Model May Reconcile the Conflicting Findings

Papageorgiou¹

2021

Preprint

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Hox gene collinearity (HGC) is a multiscalar property of many animal phyla particularly important during embryogenesis. It relates events occurring in Hox clusters inside the chromosome DNA and embryonic tissues. These two entities differ in size by more than four orders of magnitude. HGC is observed as spatial collinearity (SC) where the Hox genes are located in the order H1, H2, H3 … along the 3’ to 5’ direction of the DNA sequence. The corresponding embryonic tissues (E1, E2, E3, …) are activated along the Anterior – Posterior axis in the same order. Besides this collinearity a temporal collinearity (TC) has been also observed in many vertebrates. According to TC first is H1 expressed in E1, later is H2 in E2, followed by H3,… Lately doubt has been raised whether TC really exists. A biophysical model (BM) has been formulated and tested in the last twenty years. According to BM, physical forces are created which pull the Hox genes one after the other driving them to a transcription factory domain where they are transcribed. The existing experiments support this BM description. In the present work two equivalent realizations of BM are presented which explain the recent findings on TC as observed in the vertebrates.

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Section: A)the Traditional Approachmentioning

confidence: 99%

Section: A)the Traditional Approachmentioning

confidence: 99%

Section: A)the Traditional Approachmentioning

confidence: 99%

Section: A)the Traditional Approachmentioning

confidence: 99%

See 2 more Smart Citations

Recent Experiments Raised Doubt On the Vertebrate Temporal Collinearity of the Hox Genes. A Biophysical Model May Reconcile the Conflicting Findings

Papageorgiou¹

2021

Preprint

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“…In fact, the region is a “hotspot” for RNA-RNA interactions as identified by computational prediction querying HOTAIR against the entire mRNA transcriptome(22). Interestingly, this “hotspot” overlaps a region within HOTAIR that was found to be conserved across vertebrates (except teleosts) with potential for RNA-RNA interaction with a HOXD transcript(23). HOTAIR RNA-RNA interaction was discovered due to its association with the RNA binding protein (RBP), heterogenous nuclear ribonucleoprotein (hnRNP) B1.…”

Section: Introductionmentioning

confidence: 99%

RNA matchmaking remodels lncRNA structure and promotes PRC2 activity

Balas

Hartwick

Barrington

et al. 2020

Preprint

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Polycomb Repressive Complex 2 (PRC2) contributes to initiation of heterochromatin through catalysis of histone H3 lysine 27 (H3K27) methylation. Human PRC2 can work productively with specific long noncoding RNAs (lncRNAs) at certain target loci, yet the underlying mechanism is unclear. In apparent contradiction to lncRNA-mediated PRC2 activity, PRC2 binds to RNA in a low-specificity, high-affinity manner, effectively competing with chromatin and making RNA a potent catalytic inhibitor of H3K27 methylation activity. We address this contradiction by testing the model that intermolecular RNA-RNA interactions between the lncRNA HOTAIR and its target genes can generate a context that is favorable for PRC2 activity. This RNA matchmaking activity is promoted by the heterogenous nuclear ribonucleoprotein (hnRNP) B1, which uses multiple protein domains to bind to specific regions of HOTAIR via multi-valent protein-RNA interactions. Using chemical probing, we find that RNA-RNA interaction and B1 binding facilitate RNA structural changes in HOTAIR. Finally, we demonstrate that RNA-RNA matches of HOTAIR with target gene RNAs can relieve the inhibitory effect of a single lncRNA for PRC2 activity.By dissecting molecular details of RNA matchmaking within the HOTAIR mechanism, we highlight a switch that can occur as PRC2 samples RNA interactions broadly in the nucleus, being activated on chromatin by specific RNA matches. This concept may generalize to many contexts where RNA plays a role in potentiating PRC2 activity.

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A standardised nomenclature for long non‐coding RNAs

Seal

Bruford

2022

IUBMB Life

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The HUGO Gene Nomenclature Committee (HGNC) is the sole group with the authority to approve symbols for human genes, including long non‐coding RNA (lncRNA) genes. Use of approved symbols ensures that publications and biomedical databases are easily searchable and reduces the risks of confusion that can be caused by using the same symbol to refer to different genes or using many different symbols for the same gene. Here, we describe how the HGNC names lncRNA genes and review the nomenclature of the seven lncRNA genes most mentioned in the scientific literature.

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Ancestrally Duplicated Conserved Noncoding Element Suggests Dual Regulatory Roles of HOTAIR in cis and trans

Cited by 13 publications

References 59 publications

Recent Experiments Raised Doubt On the Vertebrate Temporal Collinearity of the Hox Genes. A Biophysical Model May Reconcile the Conflicting Findings

Recent Experiments Raised Doubt On the Vertebrate Temporal Collinearity of the Hox Genes. A Biophysical Model May Reconcile the Conflicting Findings

RNA matchmaking remodels lncRNA structure and promotes PRC2 activity

A standardised nomenclature for long non‐coding RNAs

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