| RRC ID |
44390
|
| 著者 |
Feng X, Shikama Y, Shichishima T, Noji H, Ikeda K, Ogawa K, Kimura H, Takeishi Y, Kimura J.
|
| タイトル |
Impairment of FOS mRNA stabilization following translation arrest in granulocytes from myelodysplastic syndrome patients.
|
| ジャーナル |
PLoS One
|
| Abstract |
Although quantitative and qualitative granulocyte defects have been described in myelodysplastic syndromes (MDS), the underlying molecular basis of granulocyte dysfunction in MDS is largely unknown. We recently found that FOS mRNA elevation under translation-inhibiting stimuli was significantly smaller in granulocytes from MDS patients than in healthy individuals. The aim of this study is to clarify the cause of the impaired FOS induction in MDS. We first examined the mechanisms of FOS mRNA elevation using granulocytes from healthy donors cultured with the translation inhibitor emetine. Emetine increased both transcription and mRNA stability of FOS. p38 MAPK inhibition abolished the emetine-induced increase of FOS transcription but did not affect FOS mRNA stabilization. The binding of an AU-rich element (ARE)-binding protein HuR to FOS mRNA containing an ARE in 3'UTR was increased by emetine, and the knockdown of HuR reduced the FOS mRNA stabilizing effect of emetine. We next compared the emetine-induced transcription and mRNA stabilization of FOS between MDS patients and healthy controls. Increased rates of FOS transcription by emetine were similar in MDS and controls. In the absence of emetine, FOS mRNA decayed to nearly 17% of initial levels in 45 min in both groups. In the presence of emetine, however, 76.7±19.8% of FOS mRNA remained after 45 min in healthy controls, versus 37.9±25.5% in MDS (P<0.01). To our knowledge, this is the first report demonstrating attenuation of stress-induced FOS mRNA stabilization in MDS granulocytes.
|
| 巻・号 |
8(4)
|
| ページ |
e61107
|
| 公開日 |
2013-1-1
|
| DOI |
10.1371/journal.pone.0061107
|
| PII |
PONE-D-12-37576
|
| PMID |
23593403
|
| PMC |
PMC3625160
|
| MeSH |
3' Untranslated Regions / genetics
Adult
Aged
Aged, 80 and over
Base Sequence
Case-Control Studies
ELAV Proteins / metabolism
Emetine / pharmacology
Female
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Granulocytes / drug effects
Granulocytes / enzymology
Granulocytes / metabolism*
Humans
Lipopolysaccharides / pharmacology
Male
Middle Aged
Molecular Sequence Data
Myelodysplastic Syndromes / genetics*
Protein Binding / drug effects
Protein Binding / genetics
Protein Biosynthesis* / drug effects
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-fos / biosynthesis*
Proto-Oncogene Proteins c-fos / genetics*
RNA Stability / drug effects
RNA Stability / genetics*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Transcription, Genetic / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism
|
| IF |
2.74
|
| 引用数 |
2
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HL60(RCB0041) |
