English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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  MFGE8  and  ABHD2  (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 ( CARMAL/ RP11-326A19.4/AC013565) abutting the CARMA region. Expression-genotype correlation analyses of public databases indicate that  CARMAL  levels are influenced by CAD associated variants suggesting that it might have cardioprotective functions. We found  CARMAL  to be stably expressed at relatively low levels and enriched in the cytosol.  CARMAL  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  CARMAL  (3–4×) obtained via CRISPRa using distinct single-guided RNAs did not result in consistent transcriptome effects. By contrast,  CARMAL  deletion or reduced  CARMAL  expression via CRISPRi increased  MFGE8  levels, suggesting that  CARMAL  is contributing to reduce  MFGE8  expression under basal conditions. While future investigations are required to clarify the mechanism(s) by which  CARMAL  acts on  MFGE8 , integrative bioinformatic analyses of the transcriptome of  CARMAL  deleted cells suggest that this locus may also be involved in leucine metabolism, splicing, transcriptional regulation and Shwachman-Bodian-Diamond syndrome protein function.

CARMAL Is a Long Non-coding RNA Locus That Regulates MFGE8 Expression