Posttranslational Regulation

Noncoding No More

Science Signaling  20 Jul 2010:
Vol. 3, Issue 131, pp. ec219
DOI: 10.1126/scisignal.3131ec219

So-called long “noncoding” RNAs (ncRNAs) are transcripts that are larger than small regulatory RNAs, such as microRNAs (miRNAs) and small nucleolar RNAs (snoRNAs), that have traditionally been thought not to encode proteins because they contain only short open reading frames (sORFs). Recent studies, however, have indicated that some sORFs of long ncRNAs are translated. One such translated long ncRNA is that transcribed from the polished rice (pri) locus in the fruit fly Drosophila melanogaster, which encodes four peptides 11 to 32 amino acids in length. Loss-of-function mutations in pri phenocopy loss of shavenbaby (svb), which encodes a transcription factor required for formation of hairs called trichomes on the dorsal epidermis of the fly embryo. Kondo et al. report that, in pri mutants, expression of svb was normal, but expression of genes and reporters activated by Svb was reduced. The svb locus encodes three transcription factor isoforms that share the same DNA binding and transcriptional activation domains: OvoB, the shortest isoform, is a transcriptional activator that induced trichomes when misexpressed in embryos; OvoA contains an N-terminal extension that converts it into a transcriptional repressor and could not induce ectopic trichomes; Svb also contains an N-terminal extension but induced ectopic trichomes when overexpressed. pri was required for the ability of Svb to induce ectopic trichomes but was not required for OvoB to induce extra trichomes. During development, pri expression coincided with a change in the subcellular distribution of Svb from subnuclear foci (similar to that of the OvoA repressor) to diffuse nuclear distribution (similar to that of the OvoB activator). In experiments using a reporter gene in cultured S2 cells, the presence of pri converted Svb from an OvoA-like transcriptional repressor to an OvoB-like transcriptional activator. Western blots of S2 cell extracts indicated that pri induced cleavage of the Svb N-terminal domain, thus converting it from a transcriptional repressor into an activator. The mechanism by which Pri peptides induce cleavage of Svb has not yet been determined, but the production of small peptides from polycistronic RNAs is a previously unappreciated form of posttranslational regulation that is likely to be widespread throughout eukaryotes. A Perspective by Rosenberg and Desplan addresses the evolvability of such sORFs and the difficulty of identifying them from genome sequence alone.

T. Kondo, S. Plaza, J. Zanet, E. Benrabah, P. Valenti, Y. Hashimoto, S. Kobayashi, F. Payre, Y. Kageyama, Small peptides switch the transcriptional activity of Shavenbaby during Drosophila embryogenesis. Science 329, 336–339 (2010). [Abstract] [Full Text]

M. I. Rosenberg, C. Desplan, Hiding in plain sight. Science 329, 284–285 (2010). [Summary] [Full Text]