Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs. / Nguyen, Giang Huong; Tang, Weiliang; Robles, Ana I; Beyer, Richard P; Gray, Lucas T; Welsh, Judith A; Schetter, Aaron J; Kumamoto, Kensuke; Wang, Xin Wei; Hickson, Ian D; Maizels, Nancy; Monnat, Raymond J; Harris, Curtis C.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 27, 08.07.2014, p. 9905-10.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs
AU - Nguyen, Giang Huong
AU - Tang, Weiliang
AU - Robles, Ana I
AU - Beyer, Richard P
AU - Gray, Lucas T
AU - Welsh, Judith A
AU - Schetter, Aaron J
AU - Kumamoto, Kensuke
AU - Wang, Xin Wei
AU - Hickson, Ian D
AU - Maizels, Nancy
AU - Monnat, Raymond J
AU - Harris, Curtis C
PY - 2014/7/8
Y1 - 2014/7/8
N2 - Bloom syndrome is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition, and caused by mutations in the gene encoding the Bloom syndrome, RecQ helicase-like (BLM) protein. To determine whether altered gene expression might be responsible for pathological features of Bloom syndrome, we analyzed mRNA and microRNA (miRNA) expression in fibroblasts from individuals with Bloom syndrome and in BLM-depleted control fibroblasts. We identified mRNA and miRNA expression differences in Bloom syndrome patient and BLM-depleted cells. Differentially expressed mRNAs are connected with cell proliferation, survival, and molecular mechanisms of cancer, and differentially expressed miRNAs target genes involved in cancer and in immune function. These and additional altered functions or pathways may contribute to the proportional dwarfism, elevated cancer risk, immune dysfunction, and other features observed in Bloom syndrome individuals. BLM binds to G-quadruplex (G4) DNA, and G4 motifs were enriched at transcription start sites (TSS) and especially within first introns (false discovery rate ≤ 0.001) of differentially expressed mRNAs in Bloom syndrome compared with normal cells, suggesting that G-quadruplex structures formed at these motifs are physiologic targets for BLM. These results identify a network of mRNAs and miRNAs that may drive the pathogenesis of Bloom syndrome.
AB - Bloom syndrome is a rare autosomal recessive disorder characterized by genetic instability and cancer predisposition, and caused by mutations in the gene encoding the Bloom syndrome, RecQ helicase-like (BLM) protein. To determine whether altered gene expression might be responsible for pathological features of Bloom syndrome, we analyzed mRNA and microRNA (miRNA) expression in fibroblasts from individuals with Bloom syndrome and in BLM-depleted control fibroblasts. We identified mRNA and miRNA expression differences in Bloom syndrome patient and BLM-depleted cells. Differentially expressed mRNAs are connected with cell proliferation, survival, and molecular mechanisms of cancer, and differentially expressed miRNAs target genes involved in cancer and in immune function. These and additional altered functions or pathways may contribute to the proportional dwarfism, elevated cancer risk, immune dysfunction, and other features observed in Bloom syndrome individuals. BLM binds to G-quadruplex (G4) DNA, and G4 motifs were enriched at transcription start sites (TSS) and especially within first introns (false discovery rate ≤ 0.001) of differentially expressed mRNAs in Bloom syndrome compared with normal cells, suggesting that G-quadruplex structures formed at these motifs are physiologic targets for BLM. These results identify a network of mRNAs and miRNAs that may drive the pathogenesis of Bloom syndrome.
U2 - 10.1073/pnas.1404807111
DO - 10.1073/pnas.1404807111
M3 - Journal article
C2 - 24958861
VL - 111
SP - 9905
EP - 9910
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 27
ER -
ID: 119170377