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Publication : Modified U1 snRNA suppresses expression of a targeted endogenous RNA by inhibiting polyadenylation of the transcript.

First Author  Liu P Year  2004
Journal  Nucleic Acids Res Volume  32
Issue  4 Pages  1512-7
PubMed ID  14999093 Mgi Jnum  J:88896
Mgi Id  MGI:3037402 Doi  10.1093/nar/gkh316
Citation  Liu P, et al. (2004) Modified U1 snRNA suppresses expression of a targeted endogenous RNA by inhibiting polyadenylation of the transcript. Nucleic Acids Res 32(4):1512-7
abstractText  We have previously demonstrated that a modified U1 snRNA inhibits expression of a number of targeted transgenes. Here we exploit the ability of the modified U1 snRNA to inhibit endogenous gene expression and define the mechanism responsible for this inhibitory action. MC3T3-E1 cells stably transfected with U1 anti-Cbfa1 show a change of morphology from polygonal to fibroblast-like cells. This visual observation was supported by an 80% reduction of Cbfa1 expression and suppression of downstream genes associated with osteoblast differentiation. In rat ROS 17/2.8 cells, osteocalcin and Col1a1 gene expression was reduced up to 90% by the U1 anti-osteocalcin or U1 anti-Col1a1 construct, respectively. The length of mature osteocalcin mRNA poly(A) tail was significantly shortened in the targeted mRNA by transcript-specific poly(A) test (PAT)-PCR. These data demonstrate that the modified U1 snRNA is able to reduce endogenous gene expression by limiting the polyadenylation of the targeted pre-mRNA transcript.
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