Cited by 199Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsNuclear Structure and Function

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Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.

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Murano, S, Thweatt, R, Shmookler Reis, R J, Jones, R A, Moerman, E J, Goldstein, S·1991·Molecular and Cellular Biology

DOI 10.1128/mcb.11.8.3905PMC PMC361182

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Abstract

Genes that play a role in the senescent arrest of cellular replication are likely to be overexpressed in human diploid fibroblasts (HDF) derived from subjects with Werner syndrome (WS) because these cells have a severely curtailed replicative life span. To identify some of these genes, a cDNA library was constructed from WS HDF after they had been serum depleted and repleted (5 days in medium containing 1% serum followed by 24 h in medium containing 20% serum). Differential screening of 7,500 colonies revealed 102 clones that hybridized preferentially with [32P]cDNA derived from RNA of WS cells compared with [32P]cDNA derived from normal HDF. Cross-hybridization and partial DNA sequence determination identified 18 independent gene sequences, 9 of them known and 9 unknown. The known genes included alpha 1(I) procollagen, alpha 2(I) procollagen, fibronectin, ferritin heavy chain, insulinlike growth factor-binding protein-3 (IGFBP-3), osteonectin, human tissue plasminogen activator inhibitor type I, thrombospondin, and alpha B-crystallin. The nine unknown clones included two novel gene sequences and seven additional sequences that contained both novel segments and the Alu class of repetitive short interspersed nuclear elements; five of these seven Alu+ clones also contained the long interpersed nuclear element I (KpnI) family of repetitive elements. Northern (RNA) analysis, using the 18 sequences as probes, showed higher levels of these mRNAs in WS HDF than in normal HDF. Five selected mRNAs studied in greater detail [alpha 1(I) procollagen, fibronectin, insulinlike growth factor-binding protein-3, WS3-10, and WS9-14] showed higher mRNA levels in both WS and late-passage normal HDF than in early-passage normal HDF at various intervals following serum depletion/repletion and after subculture and growth from sparse to high-density confluent arrest. These results indicate that senescence of both WS and normal HDF is accompanied by overexpression of similar sets of diverse genes which may play a role in the senescent arrest of cellular replication and in the genesis of WS, normal biological aging, and attendant diseases.

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Authors: Murano, S., Thweatt, R., Shmookler Reis, R. J., Jones, R. A., Moerman, E. J., & Goldstein, S.
Affiliations: University of Arkansas for Medical Sciences (US)
ORCID: Goldstein, S
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1991-08
Volume: 11
Issue: 8
Pages: 3905-3914
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.11.8.3905
PMC: PMC361182
OpenAlex: W2150967453
Cited by: 199
References: 88
Citations by year: 2023: 3 · 2022: 1 · 2021: 5 · 2020: 5 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 3
FWCI: 14.45
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: University of Arkansas
Arkansas Science and Technology Authority
University of Arkansas for Medical Sciences
National Institutes of Health (5r01ag008708-05)
National Institute on Aging (AG08708)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords: Werner syndrome, human diploid fibroblasts, novel gene sequences, Alu repetitive elements, long interspersed nuclear elements, fibronectin, insulin-like growth factor binding protein-3, thrombospondin, alphaB-crystallin, biological aging
MeSH terms: Base Sequence, Cell Division, Cells, Cultured, DNA, Fibroblasts, Genes, Humans, Molecular Sequence Data, Proteins, RNA, RNA, Messenger, Skin, Werner Syndrome, Blotting, Northern, Oligonucleotide Probes, Gene Library, Gene Expression

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Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.

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