Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression

Fang, Ke; Huang, Wei; Sun, Yu-Meng; Chen, Tian-Qi; Zeng, Zhan-Cheng; Yang, Qianqian; Pan, Qi; Han, Cai; Sun, Lin-Yu; Luo, Xue-Qun; Wang, Wen-Tao; Chen, Yue‐Qin

doi:10.1186/s13059-020-02186-x

Cited by 18 publications

(14 citation statements)

References 70 publications

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“…Additionally, Fang et al. ( 160 ) found that eRNAs such as SEELA are widely activated in mixed-lineage leukaemia and demonstrated that SEELA directly binds to amino acid K31 of histone 4 and mediates the cis-activated transcription of the neighboring oncogene serine incorporate 2, which regulates oncogene transcription and tumour metabolism (sphingolipid synthesis) to influence leukaemia progression. The demethylation of vascular endothelial growth factor A (VEGFA) enhancer in CML promotes the overexpression of cancer signature genes.…”

Section: Resultsmentioning

confidence: 99%

Inflammatory Immune-Associated eRNA: Mechanisms, Functions and Therapeutic Prospects

Wan

Meng

et al. 2022

Front. Immunol.

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The rapid development of multiple high-throughput sequencing technologies has made it possible to explore the critical roles and mechanisms of functional enhancers and enhancer RNAs (eRNAs). The inflammatory immune response, as a fundamental pathological process in infectious diseases, cancers and immune disorders, coordinates the balance between the internal and external environment of the organism. It has been shown that both active enhancers and intranuclear eRNAs are preferentially expressed over inflammation-related genes in response to inflammatory stimuli, suggesting that enhancer transcription events and their products influence the expression and function of inflammatory genes. Therefore, in this review, we summarize and discuss the relevant inflammatory roles and regulatory mechanisms of eRNAs in inflammatory immune cells, non-inflammatory immune cells, inflammatory immune diseases and tumors, and explore the potential therapeutic effects of enhancer inhibitors affecting eRNA production for diseases with inflammatory immune responses.

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Section: Resultsmentioning

confidence: 99%

Inflammatory Immune-Associated eRNA: Mechanisms, Functions and Therapeutic Prospects

Wan

Meng

et al. 2022

Front. Immunol.

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“…Protein recombination and purification were performed as described previously 22 , 38 . Briefly, recombinant proteins were expressed in E. coli strain BL21 [Transetta (DE3) chemically competent cell (Transgen biotech, CD801)].…”

Section: Methodsmentioning

confidence: 99%

The snoRNA-like lncRNA LNC-SNO49AB drives leukemia by activating the RNA-editing enzyme ADAR1

et al. 2022

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Long noncoding RNAs (lncRNAs) are usually 5′ capped and 3′ polyadenylated, similar to most typical mRNAs. However, recent studies revealed a type of snoRNA-related lncRNA with unique structures, leading to questions on how they are processed and how they work. Here, we identify a novel snoRNA-related lncRNA named LNC-SNO49AB containing two C/D box snoRNA sequences, SNORD49A and SNORD49B; and show that LNC-SNO49AB represents an unreported type of lncRNA with a 5′-end m7G and a 3′-end snoRNA structure. LNC-SNO49AB was found highly expressed in leukemia patient samples, and silencing LNC-SNO49AB dramatically suppressed leukemia progression in vitro and in vivo. Subcellular location indicated that the LNC-SNO49AB is mainly located in nucleolus and interacted with the nucleolar protein fibrillarin. However, we found that LNC-SNO49AB does not play a role in 2′-O-methylation regulation, a classical function of snoRNA; instead, its snoRNA structure affected the lncRNA stability. We further demonstrated that LNC-SNO49AB could directly bind to the adenosine deaminase acting on RNA 1(ADAR1) and promoted its homodimerization followed by a high RNA A-to-I editing activity. Transcriptome profiling shows that LNC-SNO49AB and ADAR1 knockdown respectively share very similar patterns of RNA modification change in downstream signaling pathways, especially in cell cycle pathways. These findings suggest a previously unknown class of snoRNA-related lncRNAs, which function via a manner in nucleolus independently on snoRNA-guide rRNA modification. This is the first report that a lncRNA regulates genome-wide RNA A-to-I editing by enhancing ADAR1 dimerization to facilitate hematopoietic malignancy, suggesting that LNC-SNO49AB may be a novel target in therapy directed to leukemia.

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“…LncRNAs can play a role in cancer development by directing histone-modifying enzymes to regulate the methylation and acetylation status of histones and cis-regulating the expression of nearby genes ( 24 , 98 , 99 ). For example, lncRNA EZR-AS1 recruits H3K4 methyltransferase SMYD3 to catalyze Tri-methylation of lysine 4 on histone H3 (H3K4me3) at the EZR promoter.…”

Section: Lncrnas Regulate Other Epigenetic Modalities Through Rbpsmentioning

confidence: 99%

Long non‑coding RNAs interact with RNA‑binding proteins to regulate genomic instability in cancer cells (Review)

2022

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Genomic instability, a feature of most cancers, contributes to malignant cell transformation and cancer progression due to the accumulation of genetic alterations. Genomic instability is reflected at numerous levels, from single nucleotide to the chromosome levels. However, the exact molecular mechanisms and regulators of genomic instability in cancer remain unclear. Growing evidence indicates that the binding of long non-coding RNAs (lncRNAs) to protein chaperones confers a variety of regulatory functions, including managing of genomic instability. The aim of the present review was to examine the roles of mitosis, telomeres, DNA repair, and epigenetics in genomic instability, and the mechanisms by which lncRNAs regulate them by binding proteins in cancer cells. This review contributes to our understanding of the role of lncRNAs and genomic instability in cancer and can potentially provide entry points and molecular targets for cancer therapies. Contents1. Introduction 2. LncRNAs affect chromosome instability via RBPs 3. LncRNAs are involved in DNA repair through RBPs 4. LncRNAs regulate other epigenetic modalities through RBPs 5.

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Cis-acting lnc-eRNA SEELA directly binds histone H4 to promote histone recognition and leukemia progression

Cited by 18 publications

References 70 publications

Inflammatory Immune-Associated eRNA: Mechanisms, Functions and Therapeutic Prospects

Inflammatory Immune-Associated eRNA: Mechanisms, Functions and Therapeutic Prospects

The snoRNA-like lncRNA LNC-SNO49AB drives leukemia by activating the RNA-editing enzyme ADAR1

Long non‑coding RNAs interact with RNA‑binding proteins to regulate genomic instability in cancer cells (Review)

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