RNA Viruses: RNA Roles in Pathogenesis, Coreplication and Viral Load

Poltronieri, Palmiro; Sun, Binlian; Mallardo, Massimo

Inhibition of RT activity in cancer cell lines, either by LINE-1-specific RNA interference or by RT inhibitory drugs, was found to reduce proliferation and promote differentiation and to antagonize tumor growth in animal models. Using CsCl density gradients, Alu-and LINE-1-containing DNA:RNA hybrid structures were identified in cancer yet not in normal cell lines [8] . In cancer cells the highly abundant RT activity intercepts various RNA classes and reverse transcribes them generating RNA:DNA hybrids. This may impair the formation of double-stranded RNAs required in the production of small regulatory RNAs (miRNA in particular), with a direct impact on gene expression. RT inhibition restores the 'normal' small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposonencoded RT drives a previously unrecognized mechanism crucial to the transformed state in tumor cells.