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Syntenic lncRNA locus exhibits DNA regulatory functions with sequence evolution
Gyan Ranjan1, Vinod Scaria2, Sridhar Sivasubbu2
1CSIR Institute of Genomics and Integrative Biology, Mathura Road, Delhi 110024, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Syntenic long non-coding RNAs (lncRNAs) maintain conserved functions across species, despite sequence divergence. These RNA loci regulate gene expression through cis-regulatory elements, contributing to vertebrate evolution.
Area of Science:
- Genomics
- Evolutionary Biology
- Molecular Biology
Background:
- Syntenic long non-coding RNAs (lncRNAs) exhibit low sequence conservation across species, raising questions about their functional relevance.
- Understanding the functional signatures of lncRNAs shared between species is crucial for evolutionary and developmental studies.
Purpose of the Study:
- To investigate the functional characteristics of syntenic lncRNAs between humans and zebrafish.
- To explore the roles of these lncRNAs in gene regulation during development and across different cell types.
Main Methods:
- Comparative analysis of syntenic lncRNA expression patterns in zebrafish and human embryonic stem cells (H1-hESC).
- Identification and characterization of cis-regulatory elements and transposable elements (TEs) within syntenic lncRNA loci.
- Examination of lncRNA locus function as repressors, enhancers, or transcription start sites (TSS) for protein-coding genes.
Main Results:
- Syntenic lncRNAs are highly expressed in zebrafish, predominantly located near protein-coding genes.
- lncRNA loci are enriched with cis-regulatory repressor signatures in early development (zebrafish) and H1-hESCs, impacting development-associated genes.
- In later developmental stages and human cell lines, these loci function as enhancers or TSS for protein-coding genes.
- Human syntenic lncRNAs are enriched in simple repeat elements, while zebrafish counterparts show LTR element enrichment, suggesting sequence evolution driven by cis-regulatory function.
Conclusions:
- Syntenic lncRNA loci possess conserved functions across vertebrate species, mediated by DNA elements, despite significant sequence divergence.
- Evolutionary changes in TE content within lncRNA loci may contribute to novel cis-regulatory functions and vertebrate innovation.
- This study underscores the importance of functional conservation over sequence conservation for lncRNAs in evolution.
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