In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 19, No. 7 ( 2023-7-18), p. e1010856-
Abstract:
Premature telomere shortening is a known factor correlated to idiopathic pulmonary fibrosis (IPF) occurrence, which is a chronic, progressive, age-related disease with high mortality. The etiology of IPF is still unknown. Here, we found that UBQLN1 plays a key role in telomere length maintenance and is potentially relevant to IPF. UBQLN1 involves in DNA replication by interacting with RPA1 and shuttling it off from the replication fork. The deficiency of UBQLN1 retains RPA1 at replication fork, hinders replication and thus causes cell cycle arrest and genome instability. Especially at telomere regions of the genome, where more endogenous replication stress exists because of G rich sequences, UBQLN1 depletion leads to rapid telomere shortening in HeLa cells. It revealed that UBQLN1 depletion also shortens telomere length at mouse lung and accelerates mouse lung fibrosis. In addition, the UBQLN1 expression level in IPF patients is downregulated and correlated to poor prognosis. Altogether, these results uncover a new role of UBQLN1 in ensuring DNA replication and maintaining telomere stability, which may shed light on IPF pathogenesis and prevention.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010856
DOI:
10.1371/journal.pgen.1010856.g001
DOI:
10.1371/journal.pgen.1010856.g002
DOI:
10.1371/journal.pgen.1010856.g003
DOI:
10.1371/journal.pgen.1010856.g004
DOI:
10.1371/journal.pgen.1010856.g005
DOI:
10.1371/journal.pgen.1010856.g006
DOI:
10.1371/journal.pgen.1010856.g007
DOI:
10.1371/journal.pgen.1010856.s001
DOI:
10.1371/journal.pgen.1010856.s002
DOI:
10.1371/journal.pgen.1010856.s003
DOI:
10.1371/journal.pgen.1010856.s004
DOI:
10.1371/journal.pgen.1010856.s005
DOI:
10.1371/journal.pgen.1010856.s006
DOI:
10.1371/journal.pgen.1010856.s007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2186725-2
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