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Cell Based Assays of SINEUP Non-coding RNAs That Can Specifically Enhance mRNA Translation
Published on: February 1, 2019
DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse
Martin M Corcoran1, Marianne Hammarsund, Chaoyong Zhu
1Molecular Biology Laboratory, Royal Bournemouth Hospital, Bournemouth, United Kingdom.
Abstract:
Our group previously identified two novel genes, RFP2/LEU5 and DLEU2, within a 13q14.3 genomic region of loss seen in various malignancies. However, no specific inactivating mutations were found in these or other genes in the vicinity of the deletion, suggesting that a nonclassical tumor-suppressor mechanism may be involved. Here, we present data showing that the DLEU2 gene encodes a putative noncoding antisense RNA, with one exon directly overlapping the first exon of the RFP2/LEU5 gene in the opposite orientation. In addition, the RFP2/LEU5 transcript can be alternatively spliced to produce either several monocistronic transcripts or a putative bicistronic transcript encoding two separate open-reading frames, adding to the complexity of the locus. The finding that these gene structures are conserved in the mouse, including the putative bicistronic RFP2/LEU5 transcript as well as the antisense relationship with DLEU2, further underlines the significance of this unusual organization and suggests a biological function for DLEU2 in the regulation of RFP2/LEU5.
Insights
The DLEU2 gene produces a noncoding antisense RNA that overlaps the RFP2/LEU5 gene. This antisense RNA may regulate RFP2/LEU5, suggesting a novel tumor-suppressor mechanism in malignancies.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Two novel genes, RFP2/LEU5 and DLEU2, were identified in a 13q14.3 genomic region frequently lost in malignancies.
- No inactivating mutations were found, suggesting nonclassical tumor-suppressor mechanisms.
Purpose of the Study:
- To investigate the function of DLEU2 and RFP2/LEU5 in the 13q14.3 region.
- To elucidate the complex gene organization and potential regulatory relationships.
Main Methods:
- Analysis of gene structure and alternative splicing of RFP2/LEU5.
- Identification and characterization of the DLEU2 transcript as a noncoding antisense RNA.
- Comparative analysis of gene structures in human and mouse genomes.
Main Results:
- DLEU2 encodes a putative noncoding antisense RNA.
- DLEU2's exon overlaps RFP2/LEU5's first exon in an antisense orientation.
- RFP2/LEU5 exhibits complex alternative splicing, producing monocistronic and bicistronic transcripts.
- Conserved gene organization and antisense relationship in mice suggest biological significance.
Conclusions:
- The DLEU2 gene encodes a noncoding antisense RNA with a regulatory role over RFP2/LEU5.
- The unusual gene organization and antisense relationship suggest a novel mechanism for tumor suppression.
- Further research into DLEU2 and RFP2/LEU5 is warranted to understand their role in cancer.
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