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. |