The RNA-binding protein La contributes to cell proliferation and CCND1 expression.
The La protein is an essential RNA-binding protein implicated in different aspects of RNA metabolism. Herein, we report that small interfering (siRNA)-mediated La depletion reduces cell proliferation of different cell lines concomitant with a reduction in cyclin D1 (CCND1) protein. To exclude off-target effects we demonstrate that exogenous La expression in La-depleted cells restores cell proliferation and CCND1 protein levels. In contrast, proliferation of immortalized CCND1 knockout cells is not affected by La depletion, supporting a functional coherence between La, CCND1 and proliferation. Furthermore, we document by reversible in vivo crosslinking and ribonucleoprotein (RNP) immunoprecipitation an association of the La protein with CCND1 messengerRNA and that CCND1 internal ribosome entry site (IRES)-dependent translation is modulated by La protein level within the cell. In addition, we show elevated La protein expression in cervical cancer tissue and its correlation with aberrant CCND1 protein levels in cervical tumor tissue lysates. In conclusion, this study establishes a role of La in cell proliferation and CCND1 expression and demonstrates for the first time an overexpression of the RNA-binding protein La in solid tumors.
Sommer
G
G
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
Dittmann
J
J
Kuehnert
J
J
Reumann
K
K
Schwartz
P E
PE
Will
H
H
Coulter
B L
BL
Smith
M T
MT
Heise
T
T
D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002469:Cell Separation; D019938:Cyclin D1 / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism*; D000097585:SS-B Antigen
D001324:Autoantigens; D019938:Cyclin D1; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C530104:CCND1 protein, human