Редактирование: GAR1

H/ACA ribonucleoprotein complex subunit 1 (Nucleolar protein family A member 1) (snoRNP protein GAR1) [NOLA1]

==Publications==

{{medline-entry
|title=Pseudouridylation defect due to [i]DKC1[/i] and [i][[NOP10]][/i] mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32554502
|abstract=RNA modifications play a fundamental role in cellular function. Pseudouridylation, the most abundant RNA modification, is catalyzed by the H/ACA small ribonucleoprotein (snoRNP) complex that shares four core proteins, dyskerin (DKC1), [[NOP10]], [[NHP2]], and [[GAR1]]. Mutations in [i]DKC1[/i], [i][[NOP10]][/i], or [i][[NHP2]][/i] cause dyskeratosis congenita (DC), a disorder characterized by telomere attrition. Here, we report a phenotype comprising nephrotic syndrome, cataracts, sensorineural deafness, enterocolitis, and early lethality in two pedigrees: males with [i]DKC1[/i] p.Glu206Lys and two children with homozygous [i][[NOP10]][/i] p.Thr16Met. Females with heterozygous [i]DKC1[/i] p.Glu206Lys developed cataracts and sensorineural deafness, but nephrotic syndrome in only one case of skewed X-inactivation. We found telomere attrition in both pedigrees, but no mucocutaneous abnormalities suggestive of DC. Both mutations fall at the dyskerin-[[NOP10]] binding interface in a region distinct from those implicated in DC, impair the dyskerin-[[NOP10]] interaction, and disrupt the catalytic pseudouridylation site. Accordingly, we found reduced pseudouridine levels in the ribosomal RNA (rRNA) of the patients. Zebrafish [i]dkc1[/i] mutants recapitulate the human phenotype and show reduced 18S pseudouridylation, ribosomal dysregulation, and a cell-cycle defect in the absence of telomere attrition. We therefore propose that this human disorder is the consequence of defective snoRNP pseudouridylation and ribosomal dysfunction.
|mesh-terms=* Animals
* Cataract
* Cell Cycle Proteins
* Child
* Enterocolitis
* Female
* Genetic Predisposition to Disease
* Hearing Loss, Sensorineural
* Humans
* Longevity
* Male
* Models, Molecular
* Molecular Dynamics Simulation
* Mutation
* Nephrotic Syndrome
* Nuclear Proteins
* Pedigree
* Protein Conformation
* RNA, Ribosomal
* Ribonucleoproteins, Small Nucleolar
* Zebrafish
|keywords=* H/ACA snoRNP
* pediatrics
* pseudouridylation
* rRNA
* telomere
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334496
}}