About this Research Topic

Background

From development to disease, long noncoding RNAs (lncRNA) act as a layer of regulation that can influence the epigenome and key biological processes including gene transcription, X-chromosome inactivation, RNA-mediated epigenetic inheritance, DNA methylation and genome stability through maintenance of active and silent chromatin state. Among the many diverse mechanisms influenced by lncRNAs, RNA-chromatin interactions are recognized as a pivotal mechanism for regulating genome stability, gene expression and nuclear function. RNA-chromatin interactions occur at specific genomic loci through direct interactions of lncRNA with protein or double-stranded DNA (dsDNA), and such interactions involve regulation by lncRNA sequence, structure and epitranscriptome. A more focused RNA-centric view of chromatin is important now more than ever before to understand unique features and mechanisms governing RNA-chromatin interactions for better understanding of lncRNA biology and therapeutics.

RNA-chromatin interactions are specifically controlled and are thought to involve lncRNA sequence, structure and epitranscriptome. We know little about what governs this specificity. Many lncRNAs are retained at specific genomic loci and exhibit function by selective interactions with either protein or dsDNA. Whether lncRNA sequence, structure and epitranscriptome, either alone or in combination, act as specific code governing RNA-chromatin interactions needs to be determined. Elucidating such an RNA-chromatin code will enable: (1) to distinguish lncRNAs working at chromatin level from those working in the cytoplasm; (2) to predict more accurately binding partners of lncRNAs regulated during development and disease; (3) to improve therapeutic targeting of RNA-chromatin complexes; (4) to accurately map novel lncRNAs that show context-dependent regulation; and (5) to assign functions to GWAS identified causal sequence variants overlapping lncRNAs. Recent advances indicate strong regulatory roles for lncRNA sequence features associated with specific RNA-protein interactions. Moreover, growing recognition for epitranscriptomics research led to the identification of epitranscriptomic marks (e.g. m6A, m5C, A-to-I RNA editing) as modulators of lncRNA interactions with chromatin. Whether lncRNA interactions with chromatin and lncRNA function are dependent on lncRNA folding influenced by sequence features and epitranscriptomic marks, needs to be determined, and doing so will provide new structural clues to improve therapeutic targeting of lncRNAs using antisense oligos (ASOs) or small molecule inhibitors. The future of lncRNA research and its therapeutic success relies heavily on elucidating the interplay between lncRNA sequence, structure and epitranscriptome and how these features, alone or in combination, stabilize RNA-chromatin interactions.

The Research Topic addresses molecular mechanisms governing RNA-chromatin interactions. We invite manuscripts of any types related to the following topics:

- RNA sequence, structure and epitranscriptome influencing RNA-chromatin interactions
- Computational tools for the prediction of lncRNA structure, epitranscriptome and RNA-binding proteins
- Role of lncRNAs and small RNAs (including miRNAs), RNA-chromatin interactions in human health and disease (fibrosis, cardiovascular, cancer and others)
- Experimental and computational methods to study RNA-chromatin interactions
- Therapeutic approaches to targeting lncRNAs and disrupting RNA-chromatin interactions (ASO, small molecule, design and considerations)
- Role of RNA modifications (e.g. m6A, m5C, A-to-I RNA editing) in RNA-dsDNA interactions
- Methods to study RNA-dsDNA interactions at genome-wide scale
- Small RNA-chromatin interactions (e.g. miRNAs, snoRNAs, scaRNAs)
- Application of single cell sequencing technologies to study RNA-chromatin interactions
- Exosomal RNA delivery and chromatin regulation
- Sex differences in lncRNA expression and RNA modifications
- Integration of epitransriptomic marks with GWAS data (e.g. m6A-QTLs)

Topic Editor Dr. Samir Ounzain is co-founder and Chief Officer of HAYA Therapeutics SA, StartLab. The other Topic Editors declare no conflict of interest in relation to the Research Topic theme

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