Abstract
RNA-binding proteins (RBPs) play a major role in many post-transcriptional processes, including mRNA stability, alternative splicing and translation. PCBP4, also called MCG10, is an RBP belonging to the poly(C)-binding protein family and a target of p53 tumor suppressor. Ectopic expression of PCBP4 induces cell-cycle arrest in G2 and apoptosis. To identify RNA targets regulated by PCBP4 and further decipher its function, we generated multiple cell lines in which PCBP4 is either inducibly over-expressed or knocked down. We found that PCBP4 expression decreases cyclin-dependent kinase inhibitor p21 induction in response to DNA damage. We also provided evidence that PCBP4 regulates p21 expression independently of p53. In addition, we showed that a deficiency in PCBP4 enhances p21 induction upon DNA damage. To validate PCBP4 regulation of p21, we made PCBP4-deficient mice and showed that p21 expression is markedly increased in PCBP4-deficient primary mouse embryo fibroblasts compared to that in wild-type counterparts. Finally, we uncovered that PCBP4 binds to the 3′-UTR of p21 transcript in vitro and in vivo to regulate p21 mRNA stability. Taken together, we revealed that PCBP4 regulates both basal and stress-induced p21 expression through binding p21 3′-UTR and modulating p21 mRNA stability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 213-224 |
| Number of pages | 12 |
| Journal | Nucleic Acids Research |
| Volume | 39 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2011 |
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ASJC Scopus subject areas
- Genetics
Cite this
The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability. / Scoumanne, Ariane; Cho, Seong Jun; Zhang, Jin; Chen, Xinbin.
In: Nucleic Acids Research, Vol. 39, No. 1, 2011, p. 213-224.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The cyclin-dependent kinase inhibitor p21 is regulated by RNA-binding protein PCBP4 via mRNA stability
AU - Scoumanne, Ariane
AU - Cho, Seong Jun
AU - Zhang, Jin
AU - Chen, Xinbin
PY - 2011
Y1 - 2011
N2 - RNA-binding proteins (RBPs) play a major role in many post-transcriptional processes, including mRNA stability, alternative splicing and translation. PCBP4, also called MCG10, is an RBP belonging to the poly(C)-binding protein family and a target of p53 tumor suppressor. Ectopic expression of PCBP4 induces cell-cycle arrest in G2 and apoptosis. To identify RNA targets regulated by PCBP4 and further decipher its function, we generated multiple cell lines in which PCBP4 is either inducibly over-expressed or knocked down. We found that PCBP4 expression decreases cyclin-dependent kinase inhibitor p21 induction in response to DNA damage. We also provided evidence that PCBP4 regulates p21 expression independently of p53. In addition, we showed that a deficiency in PCBP4 enhances p21 induction upon DNA damage. To validate PCBP4 regulation of p21, we made PCBP4-deficient mice and showed that p21 expression is markedly increased in PCBP4-deficient primary mouse embryo fibroblasts compared to that in wild-type counterparts. Finally, we uncovered that PCBP4 binds to the 3′-UTR of p21 transcript in vitro and in vivo to regulate p21 mRNA stability. Taken together, we revealed that PCBP4 regulates both basal and stress-induced p21 expression through binding p21 3′-UTR and modulating p21 mRNA stability.
AB - RNA-binding proteins (RBPs) play a major role in many post-transcriptional processes, including mRNA stability, alternative splicing and translation. PCBP4, also called MCG10, is an RBP belonging to the poly(C)-binding protein family and a target of p53 tumor suppressor. Ectopic expression of PCBP4 induces cell-cycle arrest in G2 and apoptosis. To identify RNA targets regulated by PCBP4 and further decipher its function, we generated multiple cell lines in which PCBP4 is either inducibly over-expressed or knocked down. We found that PCBP4 expression decreases cyclin-dependent kinase inhibitor p21 induction in response to DNA damage. We also provided evidence that PCBP4 regulates p21 expression independently of p53. In addition, we showed that a deficiency in PCBP4 enhances p21 induction upon DNA damage. To validate PCBP4 regulation of p21, we made PCBP4-deficient mice and showed that p21 expression is markedly increased in PCBP4-deficient primary mouse embryo fibroblasts compared to that in wild-type counterparts. Finally, we uncovered that PCBP4 binds to the 3′-UTR of p21 transcript in vitro and in vivo to regulate p21 mRNA stability. Taken together, we revealed that PCBP4 regulates both basal and stress-induced p21 expression through binding p21 3′-UTR and modulating p21 mRNA stability.
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UR - http://www.scopus.com/inward/citedby.url?scp=78651321770&partnerID=8YFLogxK
U2 - 10.1093/nar/gkq778
DO - 10.1093/nar/gkq778
M3 - Article
C2 - 20817677
AN - SCOPUS:78651321770
VL - 39
SP - 213
EP - 224
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 1
ER -