Integrated lncRNA function upon genomic and epigenomic regulation

Herman, Allison N.; Tsitsipatis, Dimitrios; Gorospe, Myriam

doi:10.1016/j.molcel.2022.05.027

Cited by 171 publications

(93 citation statements)

References 177 publications

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“…In summary, we can use this database to select certain lncRNAs to explore for specific mechanisms in cementoblast mineralization. For example, overexpression and knockdown assays are performed to clarify one of the interested lncRNAs' functions in vitro and in vivo, and to explore mechanisms of them in transcriptional, post‐transcriptional, and epigenetic levels 44,45. The findings may provide novel areas of interest for cementogenesis and periodontal regeneration.…”

Section: Discussionmentioning

confidence: 99%

Expression profile analysis of long noncoding RNA and messenger RNA during mouse cementoblast mineralization

Huang

Wang

Liao

et al. 2022

J of Periodontal Research

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Background and Objective Emerging evidence has uncovered that long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) exert biofunctions on cellular mineralization and bone formation. In this study, we aimed to identify lncRNA–mRNA expression profiles and expression patterns, and explore their underlying biofunctions during cementoblast mineralization. Materials and Methods Cementoblasts were cultured in mineralized medium for 0, 7, and 14 days. We used quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot (WB) to detect expression levels of osteocalcin (OCN), bone sialoprotein (BSP), and Osterix (Osx). Alkaline phosphatase (ALP) staining and alizarin red staining (ARS) were conducted to detect ALP activity and number of mineralized nodule. Total RNA was extracted from cells and used for high‐throughput sequencing. EBSeq package was applied to analyze differentially expressed genes. Mfuzz R package was used to identify gene expression patterns. The weighted gene co‐expression network analysis (WGCNA) was performed to explore co‐expressed mRNAs of differentially expressed lncRNAs (DElncRNAs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were adopted by Clusterprofile R package. Results Cementoblasts were successfully induced by osteogenic medium. Compared with those on day 0, 384 DElncRNAs and 4255 differentially expressed mRNAs (DEmRNAs), respectively, were found on day 7. Meanwhile, 645 DElncRNAs and 4717 DEmRNAs were detected on day 14. Both DElncRNAs and DEmRNAs were classified into six clusters with different expression patterns. DEmRNAs and co‐expressed mRNA of DElncRNAs were predominantly related to cell process, binding, phosphatidylinositol‐3 kinase (PI3K)‐Akt signaling pathway, hypoxia‐inducible factor‐1 (HIF‐1) signaling pathway, mitogen‐activated protein kinase (MAPK) signaling pathway, and hippo signaling pathway. Conclusion The results demonstrated that both noncoding and coding RNAs were involved in the process of mineralization in cementoblasts, which may provide a new database for further study.

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Section: Discussionmentioning

confidence: 99%

Expression profile analysis of long noncoding RNA and messenger RNA during mouse cementoblast mineralization

Huang

Wang

Liao

et al. 2022

J of Periodontal Research

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“…In contrast, cytoplasmic lncRNAs interact with proteins, other RNAs, or different organelles to alter mRNA stability and localization, protein translation, post-translational modification, mitochondrial functions, or protein trafficking. [9][10][11][12][13][14][15] In some cases, the act of transcription, rather than the lncRNA transcripts, is the functional entity to regulate target gene expression locally. 16 Although significant progress has been made in understanding the functions of lncRNAs in recent years, their transcription regulatory mechanism has been poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Genetic and environmental perturbations alter the rhythmic expression pattern of a circadian long non-coding RNA, Per2AS, in mouse liver

et al. 2022

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Background: Long non-coding RNAs (lncRNAs) play a wide variety of biological roles without encoding a protein. Although the functions of many lncRNAs have been uncovered in recent years, the regulatory mechanism of lncRNA expression is still poorly understood despite that the expression patterns of lncRNAs are much more specific compared to mRNAs. Here, we investigated the rhythmic expression of Per2AS, a novel lncRNA that regulates circadian rhythms. Given that Per2AS expression is antiphasic to Period2 (Per2), a core circadian clock gene, and transcribed from the antisense strand of Per2, we hypothesized that the rhythmic Per2AS expression is driven either by its own promoter or by the rhythmic Per2 transcription via transcriptional interference. Methods: We leveraged existing circadian RNA-seq datasets and analyzed the expression patterns of Per2AS and Per2 in response to the genetic or environmental disruption of the circadian rhythm in mouse liver. We tested our hypotheses by comparing the changes in the expression patterns of Per2AS and Per2. Conclusions: We found that, in some cases, Per2AS expression is independently controlled by other circadian transcription factors. In other cases, the pattern of expression change is consistent with both transcriptional interference and independent regulation hypotheses. Although additional experiments will be necessary to distinguish these possibilities, findings from this work contribute to a deeper understanding of the mechanism of how the expression of lncRNA is regulated.

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“…The vast majority of Pol II transcripts encoded by the genomes of multicellular animals correspond to long non-coding RNAs (lncRNAs), not mRNAs. Their wide distribution in the genome and the fact that their expression is often coordinated with genes in the immediate vicinity has led to the idea that they have functions in gene regulation and chromosome organization (Herman et al, 2022; Li and Fu, 2019; Núñez-Martínez and Recillas-Targa, 2022; Statello et al, 2021). Unlike the sequences of protein coding mRNAs, which are typically conserved across species, the primary sequences of lncRNAs are usually not very well conserved.…”

Section: Introductionmentioning

confidence: 99%

The insulating activity of theDrosophilaBX-C chromatin boundaryFub-1is parasegmentally regulated by lncRNA read-through

Ibragimov

Bing

Shidlovskii

et al. 2022

Preprint

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Though long non-coding RNAs (lncRNAs) represent a substantial fraction of the Pol II transcripts in multicellular animals, only a few have known functions. Here we report that the blocking activity of the Bithorax complex (BX-C) Fub-1 boundary is segmentally regulated by its own lncRNA. The Fub-1 boundary is located between the Ultrabithorax (Ubx) gene and the bxd/pbx regulatory domain, which is responsible for regulating Ubx expression in parasegment PS6/segment A1. Fub-1 consists of two hypersensitive sites, HS1 and HS2. HS1 is an insulator while HS2 functions primarily as a lncRNA promoter. To activate Ubx expression in PS6/A1 enhancers in the bxd/pbx domain must be able to bypass Fub-1 blocking activity. We show that expression of the Fub-1 lncRNAs in PS6/A1 from the HS2 promoter inactivates Fub-1 insulating activity. Inactivation is due to readthrough as the HS2 promoter must be directed towards HS1 to disrupt blocking.

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Integrated lncRNA function upon genomic and epigenomic regulation

Cited by 171 publications

References 177 publications

Expression profile analysis of long noncoding RNA and messenger RNA during mouse cementoblast mineralization

Expression profile analysis of long noncoding RNA and messenger RNA during mouse cementoblast mineralization

Genetic and environmental perturbations alter the rhythmic expression pattern of a circadian long non-coding RNA, Per2AS, in mouse liver

The insulating activity of theDrosophilaBX-C chromatin boundaryFub-1is parasegmentally regulated by lncRNA read-through

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