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Differentially expressed, variant U1 snRNAs regulate gene expression in human cells
Dawn O'Reilly1, Martin Dienstbier, Sally A Cowley
1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Genome Research
|October 17, 2012
Summary
Variant U1 small nuclear (sn)RNA genes, previously thought to be non-functional, actively regulate gene expression. These variant U1 snRNAs control pre-mRNA processing and have biological functions in vivo.
Area of Science:
- Molecular Biology
- Genetics
- RNA Biology
Background:
- Human U1 small nuclear (sn)RNA is essential for pre-mRNA splicing.
- Variant (v)U1 snRNA genes, located on chromosome 1, were historically considered pseudogenes.
- Recent findings suggest some vU1 snRNA genes produce functional transcripts.
Purpose of the Study:
- To investigate the biological function of variant U1 snRNAs.
- To identify target genes regulated by a specific vU1 snRNA.
- To explore the role of vU1 snRNAs in gene expression regulation.
Main Methods:
- Utilized antisense oligonucleotides to inhibit a specific vU1 snRNA in HeLa cells.
- Analyzed global transcriptome changes using the Affymetrix Human Exon ST 1.0 array.
- Investigated vU1 snRNA packaging into ribonucleoproteins (RNPs).
Main Results:
- A specific vU1 snRNA was found to regulate the expression of a subset of genes at the pre-mRNA processing level.
- This study provides the first evidence of a biological function for variant U1 snRNAs in vivo.
- Differential expression of vU1 snRNA genes was observed in human embryonic stem cells (hESCs) and HeLa cells.
Conclusions:
- Variant U1 snRNAs possess a regulatory role in gene expression through pre-mRNA processing.
- The packaging of vU1 snRNAs into unique RNPs suggests specialized functions.
- Differential expression patterns indicate potential developmental control of RNA processing by vU1 snRNPs.
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