Is a Long Non-coding RNA Locus That Regulates Expression.

Genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) most of them located in non-protein coding regions of the genome. One such locus is the CAD Associated Region between and (CARMA), a ∼18 kb haplotype that was recently shown to regulate vicinal protein coding genes. Here, we further investigate the region by examining a long non-coding RNA gene locus (RP11-326A19.4/AC013565) abutting the CARMA region. Expression-genotype correlation analyses of public databases indicate that levels are influenced by CAD associated variants suggesting that it might have cardioprotective functions. We found to be stably expressed at relatively low levels and enriched in the cytosol. function was investigated by several gene targeting approaches in HEK293T: inactive CRISPR fusion proteins, antisense, overexpression and inactivation by CRISPR-mediated knock-out. Modest increases in (3-4×) obtained via CRISPRa using distinct single-guided RNAs did not result in consistent transcriptome effects. By contrast, deletion or reduced expression via CRISPRi increased levels, suggesting that is contributing to reduce expression under basal conditions. While future investigations are required to clarify the mechanism(s) by which acts on , integrative bioinformatic analyses of the transcriptome of deleted cells suggest that this locus may also be involved in leucine metabolism, splicing, transcriptional regulation and Shwachman-Bodian-Diamond syndrome protein function.