https://transhumanist.ru/index.php?action=history&feed=atom&title=GAR1GAR1 - История изменений2026-06-01T00:04:30ZИстория изменений этой страницы в викиMediaWiki 1.43.6https://transhumanist.ru/index.php?title=GAR1&diff=4164&oldid=prevOdysseusBot: Новая страница: «H/ACA ribonucleoprotein complex subunit 1 (Nucleolar protein family A member 1) (snoRNP protein GAR1) [NOLA1] ==Publications== {{medline-entry |title=Pseudourid...»2021-04-29T19:03:55Z<p>Новая страница: «H/ACA ribonucleoprotein complex subunit 1 (Nucleolar protein family A member 1) (snoRNP protein GAR1) [NOLA1] ==Publications== {{medline-entry |title=Pseudourid...»</p>
<p><b>Новая страница</b></p><div>H/ACA ribonucleoprotein complex subunit 1 (Nucleolar protein family A member 1) (snoRNP protein GAR1) [NOLA1]<br />
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==Publications==<br />
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{{medline-entry<br />
|title=Pseudouridylation defect due to [i]DKC1[/i] and [i][[NOP10]][/i] mutations causes nephrotic syndrome with cataracts, hearing impairment, and enterocolitis.<br />
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32554502<br />
|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.<br />
|mesh-terms=* Animals<br />
* Cataract<br />
* Cell Cycle Proteins<br />
* Child<br />
* Enterocolitis<br />
* Female<br />
* Genetic Predisposition to Disease<br />
* Hearing Loss, Sensorineural<br />
* Humans<br />
* Longevity<br />
* Male<br />
* Models, Molecular<br />
* Molecular Dynamics Simulation<br />
* Mutation<br />
* Nephrotic Syndrome<br />
* Nuclear Proteins<br />
* Pedigree<br />
* Protein Conformation<br />
* RNA, Ribosomal<br />
* Ribonucleoproteins, Small Nucleolar<br />
* Zebrafish<br />
|keywords=* H/ACA snoRNP<br />
* pediatrics<br />
* pseudouridylation<br />
* rRNA<br />
* telomere<br />
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334496<br />
}}</div>OdysseusBot