Noncoding RNAs at Work

Science's STKE  06 Sep 2005:
Vol. 2005, Issue 300, pp. tw320
DOI: 10.1126/stke.3002005tw320

MicroRNAs (miRNAs), one type of small noncoding RNAs (ncRNAs), are about 21 nucleotides in length and are believed to regulate gene expression either through messenger RNA (mRNA) cleavage or by translational repression. Pillai et al. show that in human cells, the miRNA let-7 represses gene expression by inhibiting translation initiation of capped mRNAs rather than through a degradation mechanism. This repressive machinery appears to be localized to cytoplasmic processing (P) bodies, where mRNAs are stored or degraded. A large fraction of eukaryotic genomes are transcribed into ncRNAs, some of which, such as miRNAs or the much larger Xist ncRNA, have known functions. However, the great majority of ncRNAs are of unknown functional significance. Willingham et al. have developed a method for identifying functional ncRNAs--looking for evolutionary conservation and using a battery of cell-based RNA-interference assays--and have characterized the noncoding repressor of NFAT (NRON) that represses the transcription factor NFAT (nuclear factor of regulated T cells), probably through modulation of NFAT's cellular localization.

R. S. Pillai, S. N. Bhattacharyya, C. G. Artus, T. Zoller, N. Cougot, E. Basyuk, E. Bertrand, W. Filipowicz, Inhibition of translational initiation by let-7 microRNA in human cells. Science 309, 1573-1576 (2005). [Abstract] [Full Text]

A. T. Willingham, A. P. Orth, S. Batalov, E. C. Peters, B. G. Wen, P. Aza-Blanc, J. B. Hogenesch, P. G. Schultz, A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309, 1570-1573 (2005). [Abstract] [Full Text]