ISPO

Tranforming RNA

K Hamada, MD

Hiroshima University, Institute for Radiation biology and medicine, Hiroshima, Hiroshima Japan

A normal cell accumulates multiple uncertain alterations to become the tumorigenic cells. Such alterations might be due to perturbation of the ability of a cellular regulatory system to maintain normal responsiveness to the environment. Previously it was found that a small nuclear RNA, U5, exhibited a transforming potential when transfected into rat fibroblastic cells. In further studies, the 3' half of U5 first stem structure showed a similar transforming activity when expressed with a poly(A) tail. This noncoding RNA was capable of inducing several phenotypes leading to malignancy such as an altered morphology, an enhanced growth rate, a decreased level of extracellular matrix protein synthesis, and a disrupted gap junctional communication. The RNA was found to suppress the translation of a secretory-signal-peptide containing protein in reticulocyte lysate,blocking a physiological regulatory function played by a signal recognition particle and the ribosome. This finding suggests that the translation initiation factors may be used exclusively for the non-secretory protein synthesis. I report here that expression of the RNA results in an increased amount of the translation initiation factor eIF4E and, in turn, altered expression of Myc whose mRNA is known to possess the 5' untranslated region involved in translational efficiency. These data suggest that the transforming RNA, by itself, may not only create a cellular condition prerequisite for malignant transformation but also participate in altered expression of oncogenic proteins.

KEY WORDS: small nuclear U5 RNA, transforming potential, noncoding RNA, secretory protein synthesis, eIF-4E, Myc.

For more information, contact khamada@hiroshima-u.ac.jp

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Carcinogenesis.

http://www.cancerprev.org/Journal/Issues/26/101/1010/4283