Regulating the Regulator

Science's STKE  22 Aug 2006:
Vol. 2006, Issue 349, pp. tw285
DOI: 10.1126/stke.3492006tw285

MicroRNAs (miRNAs) have emerged as posttranscriptional regulators of gene expression that appear to have important roles in complex processes like development and the development of cancer. Although the abundance of miRNAs increases dramatically during development and is decreased in some cancer cells, how the production of miRNAs is regulated has not been known. Although transcription of miRNAs is one obvious control point, the processing steps mediated by the nuclear ribonuclease III (RNAse III) enzymes known as Drosha and Dicer might also contribute. Thomson et al. therefore monitored expression of the Let-7 family of miRNAs during mouse development. The amount of mature Let-7g increased several thousand-fold during mouse embryogenesis but was not correlated with production of the primary transcript. Rather, the change in abundance appeared more likely to reflect a block in processing of a specific group of miRNAs by Drosha. A set of genes was also identified encoding miRNAs that decreased in abundance in published tumor expression data. Again for this set of genes, there was no correlation between abundance of the primary transcript and the reduced expression of mature miRNA. The authors propose that the Drosha-mediated processing step is an important control point for modulating the abundance of miRNAs in normal and cancer cells.

J. M. Thomson, M. Newman, J. S. Parker, E. M. Morin-Kensicki, T. Wright, S. M. Hammond, Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 20, 2202-2207 (2006). [Abstract] [Full Text]