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Abstract Long noncoding RNAs (lncRNAs) are a large and diverse class of genes in eukaryotic genomes that contribute to a variety of regulatory processes. Functionally characterized lncRNAs play critical roles in plants, ranging from regulating flowering to controlling lateral root formation. However, findings from the past decade have revealed that thousands of lncRNAs are present in plant transcriptomes, and characterization has lagged far behind identification. In this setting, distinguishing function from noise is challenging. However, the plant community has been at the forefront of discovery in lncRNA biology, providing many functional and mechanistic insights that have increased our understanding of this gene class. In this review, we examine the key discoveries and insights made in plant lncRNA biology over the past two and a half decades. We describe how discoveries made in the pregenomics era have informed efforts to identify and functionally characterize lncRNAs in the subsequent decades. We provide an overview of the functional archetypes into which characterized plant lncRNAs fit and speculate on new avenues of research that may uncover yet more archetypes. Finally, this review discusses the challenges facing the field and some exciting new molecular and computational approaches that may help inform lncRNA comparative and functional analyses.
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Ectopic expression to synthetic design: Deriving engineering principles of lncRNA-mediated epigenetic regulation
A key challenge in synthetic biology is achieving durable amplification of low-level inputs in gene regulation systems. Current RNA-based tools primarily operate post-transcriptionally and often yield limited, transient responses. An underexplored feature of lowly expressed long non-coding RNAs (lncRNAs) is their ability to induce outsized effects on chromatin regulation across large genomic regions. Mechanistic insights from basic research are bringing the field closer to designing lncRNAs for epigenetic engineering. We review foundational studies on ectopic expression to uncover lncRNA-mediated epigenetic mechanisms and state-of-the-art transgenic systems for studying lncRNA-driven epigenetic regulation. We present perspectives on strategies for testing the composability of modular lncRNA elements to build rationally designed systems with programmable chromatin-modifying functions and potential biomedical applications such as gene dosage correction. Deepening mechanistic insights into lncRNA function, combined with the development of lncRNA-based technologies for genome regulation, will pave the way for significant advances in cell state control.
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- Award ID(s):
- 2243665
- PAR ID:
- 10661241
- Publisher / Repository:
- Cell Systems
- Date Published:
- Journal Name:
- Cell Systems
- Volume:
- 16
- Issue:
- 12
- ISSN:
- 2405-4712
- Page Range / eLocation ID:
- 101478
- Subject(s) / Keyword(s):
- CRISP-Disp disease modeling epigenetics long non-coding RNA nuclear chromatin synthetic biology tools therapeutics
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1016/j.cels.2025.101478
