Deciphering impact of single nucleotide polymorphisms on cotranscriptional modification in CCM gene mRNAs.
Am J Physiol Cell Physiol
; 323(4): C1274-C1284, 2022 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-36094437
ABSTRACT
Novel insights on regulation of gene expression mechanisms highlight the pivotal role of epitranscriptomic modifications on decision about transcript fate. These modifications include methylation of adenosine and cytosine in RNA molecules. Impairment of the normal epitranscriptome profile was observed in several pathological conditions, such as cancer and neurodegeneration. However, it is still unknown if alteration of this regulatory mechanism can be involved in cerebral cavernous malformation (CCM) development. CCM is a rare genetic condition affecting brain microvasculature, resulting from mutations in the three genes KRIT1, CCM2, and PDCD10. By data integration of association study, in silico prediction, and gene expression analysis, we evaluated role of single nucleotide polymorphisms (SNPs) highly recurrent in patients with CCM, on CCM gene expression regulation. Results showed that several of these SNPs lead to a drastic downexpression, in KRIT1 and CCM2 genes and this downregulation can be due to alteration of epitranscriptome profile, occurring these SNPs in gene regions that are subject to epitranscriptome modifications. These data suggest that this novel mechanism of gene expression regulation can be consider to further investigation on CCM pathogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemangioma Cavernoso do Sistema Nervoso Central
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália