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CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis
Published on: April 25, 2022
Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host-gene
Karim Rahimi1, Annette Christine Füchtbauer2, Fardin Fathi3
1Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Alle 3, 8000, Aarhus C, Denmark. karim@mbg.au.dk.
Abstract:
MicroRNAs are important regulators of cellular functions. MiR-302/367 is a polycistronic miRNA cluster that can induce and maintain pluripotency. Here we investigate the transcriptional control and the processing of the miR-302 host-gene in mice. Our results indicate that the mmu-miR-302 host-gene is alternatively spliced, polyadenylated and exported from the nucleus. The regulatory sequences extend at least 2 kb upstream of the transcription start site and contain several conserved binding sites for both transcriptional activators and repressors. The gene structure and regulatory elements are highly conserved between mouse and human. So far, regulating miR-302 expression is the only known function of the miR-302 host-gene. Even though we here only provide one example, regulation of microRNA transcription might be a so far little recognized function of long non-coding RNA genes.
Insights
This study reveals how the mouse miR-302 host gene is regulated and processed. Its regulatory elements are conserved in humans, suggesting a broader role in microRNA gene regulation.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- MicroRNAs (miRNAs) are key regulators of cellular functions.
- The miR-302/367 cluster is crucial for inducing and maintaining pluripotency.
- The transcriptional control and processing of the miR-302 host gene are not fully understood.
Purpose of the Study:
- To investigate the transcriptional control of the mouse miR-302 host gene.
- To analyze the processing mechanisms of the mmu-miR-302 host gene.
- To explore the evolutionary conservation of the miR-302 gene structure and regulatory elements.
Main Methods:
- Analysis of gene structure and alternative splicing.
- Identification of regulatory sequences and transcription factor binding sites.
- Comparative genomics between mouse and human sequences.
Main Results:
- The mmu-miR-302 host gene undergoes alternative splicing, polyadenylation, and nuclear export.
- Regulatory sequences extend over 2 kb upstream, containing conserved binding sites for transcription factors.
- The gene structure and regulatory elements show high conservation between mouse and human.
Conclusions:
- The miR-302 host gene's regulation involves complex transcriptional control and processing.
- Conserved regulatory elements suggest a significant role in miR-302 expression.
- Long non-coding RNA genes may have an under-recognized function in regulating microRNA transcription.
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