A chromatin-associated splicing isoform of OIP5-AS1 acts in cis to regulate the OIP5 oncogene
Open Access
- 6 January 2021
- journal article
- research article
- Published by Taylor & Francis Ltd in RNA Biology
- Vol. 18 (11), 1834-1845
- https://doi.org/10.1080/15476286.2021.1871816
Abstract
A large portion of the human genome is transcribed into long noncoding RNAs that can range from 200 nucleotides to several kilobases in length. The number of identified lncRNAs is still growing, but only a handful of them have been functionally characterized. However, it is known that the functions of lncRNAs are closely related to their subcellular localization. Cytoplasmic lncRNAs can regulate mRNA stability, affect translation and act as miRNA sponges, while nuclear-retained long noncoding RNAs have been reported to be involved in transcriptional control, chromosome scaffolding, modulation of alternative splicing and chromatin remodelling. Through these processes, lncRNAs have diverse regulatory roles in cell biology and diseases. OIP5-AS1 (also known as Cyrano), a poorly characterized lncRNA expressed antisense to the OIP5 oncogene, is deregulated in multiple cancers. We showed that one of the OIP5-AS1 splicing forms (ENST00000501665.2) is retained in the cell nucleus where it associates with chromatin, thus narrowing down the spectrum of its possible mechanisms of action. Its knockdown with antisense LNA gapmeRs led to inhibited expression of a sense partner, OIP5, strongly suggesting a functional coupling between OIP5 and ENST00000501665.2. A subsequent bioinformatics analysis followed by RAP-MS and RNA Immunoprecipitation experiments suggested its possible mode of action; in particular, we found that ENST00000501665.2 directly binds to a number of nuclear proteins, including SMARCA4, a component of the SWI/SNF chromatin remodelling complex, whose binding motif is located in the promoter of the OIP5 oncogene.Keywords
Funding Information
- National Science Center
This publication has 52 references indexed in Scilit:
- Long Noncoding RNAs: Past, Present, and FutureGenetics, 2013
- The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expressionGenome Research, 2012
- Fast gapped-read alignment with Bowtie 2Nature Methods, 2012
- Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and CufflinksNature Protocols, 2012
- OIP5 is a highly expressed potential therapeutic target for colorectal and gastric cancersBMB Reports, 2010
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- CPC: assess the protein-coding potential of transcripts using sequence features and support vector machineNucleic Acids Research, 2007
- Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAsCell, 2007
- Priming of Centromere for CENP-A Recruitment by Human hMis18α, hMis18β, and M18BP1Developmental Cell, 2007
- A Chromosomal Memory Triggered by Xist Regulates Histone Methylation in X InactivationPLoS Biology, 2004