TY - JOUR
T1 - Expression of the cytoplasmic nucleolin for post-transcriptional regulation of macrophage colony-stimulating factor mRNA in ovarian and breast cancer cells
AU - Woo, Ho Hyung
AU - Lee, Sang C.
AU - Gibson, Steven J.
AU - Chambers, Setsuko K.
N1 - Funding Information:
We thank Stephen Greco, Michael Diri, and Arpan Patel for technical help in preparing plasmids and cell lines. This work was supported by the Women's Cancers of the University of Arizona Cancer Center, the University of Arizona Cancer Center Support Grant P30 CA023074, and the Bobbi Olson Endowment Fund (to SKC).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - The formation of the mRNP complex is a critical component of translational regulation and mRNA decay. Both the 5' and 3'UTRs of CSF-1 mRNA are involved in post-transcriptional regulation. In CSF-1 mRNA, a small hairpin loop structure is predicted to form at the extreme 5' end (2–21 nt) of the 5'UTR. Nucleolin binds the hairpin loop structure in the 5'UTR of CSF-1 mRNA and enhances translation, while removal of this hairpin loop nucleolin binding element dramatically represses translation. Thus in CSF-1 mRNA, the hairpin loop nucleolin binding element is critical for translational regulation. In addition, nucleolin interacts with the 3'UTR of CSF-1 mRNA and facilitates the miRISC formation which results in poly (A) tail shortening. The overexpression of nucleolin increases the association of CSF-1 mRNA containing short poly (A)n ≤ 26, with polyribosomes. Nucleolin both forms an mRNP complex with the eIF4G and CSF-1 mRNA, and is co-localized with the eIF4G in the cytoplasm further supporting nucleolin's role in translational regulation. The distinct foci formation of nucleolin in the cytoplasm of ovarian and breast cancer cells implicates the translational promoting role of nucleolin in these cancers.
AB - The formation of the mRNP complex is a critical component of translational regulation and mRNA decay. Both the 5' and 3'UTRs of CSF-1 mRNA are involved in post-transcriptional regulation. In CSF-1 mRNA, a small hairpin loop structure is predicted to form at the extreme 5' end (2–21 nt) of the 5'UTR. Nucleolin binds the hairpin loop structure in the 5'UTR of CSF-1 mRNA and enhances translation, while removal of this hairpin loop nucleolin binding element dramatically represses translation. Thus in CSF-1 mRNA, the hairpin loop nucleolin binding element is critical for translational regulation. In addition, nucleolin interacts with the 3'UTR of CSF-1 mRNA and facilitates the miRISC formation which results in poly (A) tail shortening. The overexpression of nucleolin increases the association of CSF-1 mRNA containing short poly (A)n ≤ 26, with polyribosomes. Nucleolin both forms an mRNP complex with the eIF4G and CSF-1 mRNA, and is co-localized with the eIF4G in the cytoplasm further supporting nucleolin's role in translational regulation. The distinct foci formation of nucleolin in the cytoplasm of ovarian and breast cancer cells implicates the translational promoting role of nucleolin in these cancers.
KW - Cytoplasmic nucleolin
KW - Deadenylation
KW - Hairpin loop structure
KW - Macrophage colony stimulating factor (CSF-1) mRNA
KW - Translation
KW - Untranslated regions
KW - eIF4G
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U2 - 10.1016/j.bbagrm.2017.01.006
DO - 10.1016/j.bbagrm.2017.01.006
M3 - Article
C2 - 28131007
AN - SCOPUS:85010471624
VL - 1860
SP - 337
EP - 348
JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
SN - 1874-9399
IS - 3
ER -