| | |  | | | | Record from Web of Science® | | | | | | |
| RAS is regulated by the let-7 MicroRNA family |
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| Author(s): Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ |
| Source: CELL Volume: 120 Issue: 5 Pages: 635-647 Published: MAR 11 2005 |
| Times Cited: 709 References: 56 |
| Abstract: MicroRNAs (miRNAs) are regulatory RNAs found in multicellular eukaryotes, including humans, where they are implicated in cancer. The let-7 miRNA times seam cell terminal differentiation in C. elegans. Here we show that the let-7 family negatively regulates let-60/RAS. Loss of let-60/RAS suppresses let-7, and the let-60/RAS 3'UTR contains multiple let-7 complementary sites (LCSs), restricting reporter gene expression in a let-7-dependent manner. mir-84, a let-7 family member, is largely absent in vulval precursor cell P6.p at the time that let-60/RAS specifies the 1 degrees vulval fate in that cell, and mir-84 overexpression suppresses the multivulva phenotype of activating let-60/ RAS mutations. The 3'UTRs of the human RAS genes contain multiple LCSs, allowing let-7 to regulate RAS expression. let-7 expression is lower in lung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, providing a possible mechanism for let-7 in cancer. |
| Document Type: Article |
| Language: English |
| Reprint Address: Slack, FJ (reprint author), Yale Univ, Dept Mol Cellular & Dev Biol, POB 208103, New Haven, CT 06520 USA |
Addresses:
1. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
2. Ambion Inc, Austin, TX 78744 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 908EY |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2005.01.014 |
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