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Published on: April 21, 2023
Gene isoform specificity through enhancer-associated antisense transcription.
Courtney S Onodera1, Jason G Underwood, Sol Katzman
1Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, California, United States of America.
Enhancers can regulate gene expression by producing antisense RNAs, controlling specific gene versions. This newly discovered mechanism highlights lineage-specific transcriptional regulation via enhancer-associated non-coding RNAs (ncRNAs).
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Enhancers and antisense RNAs are crucial for transcriptional regulation.
- The functional role of enhancer-associated non-coding RNAs (ncRNAs) remains largely unclear.
- Understanding these interactions is key to deciphering gene expression control.
Purpose of the Study:
- To investigate the functional role of enhancer-associated antisense transcripts.
- To identify novel ncRNAs involved in gene regulation.
- To explore the mechanisms of isoform-specific gene expression control.
Main Methods:
- RNA-Sequencing of mouse embryonic stem cells (mESCs) and neural precursor cells (NPs).
- Analysis of enhancer activity and antisense RNA expression.
- Overexpression and knockdown experiments to assess functional impact.
Main Results:
- Identified two novel enhancer-associated antisense transcripts in mESCs, absent in NPs.
- Antisense RNA expression correlated with shorter isoforms of overlapping protein-coding genes (Zmynd8, Brd1).
- Demonstrated cis-acting regulatory mechanisms of antisense transcripts on sense gene isoform expression.
Conclusions:
- Enhancers can regulate isoform-specific gene expression through ncRNA intermediates.
- This mode of transcriptional regulation appears to be lineage-specific and evolved independently.
- Findings suggest a broader role for enhancer-ncRNA interactions in gene regulation across species.
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