Editors' ChoiceNONCODING RNA

Big Brother's a Bully

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Science Signaling  09 Sep 2008:
Vol. 1, Issue 36, pp. ec314
DOI: 10.1126/scisignal.136ec314

Genomes contain a combination of coding sequences that are used to create proteins and noncoding sequences that are transcribed but not translated and that regulate gene expression. The most common of these noncoding RNAs are the small regulatory RNAs, such as the small-interfering RNAs (siRNAs) and the microRNAs. However, there are also larger regulatory noncoding RNAs, although these are less well characterized than their smaller counterparts. Hellwig and Bass identified in Caenorhabditis elegans an 800-nucleotide structured transcript, which they named rncs-1 for "RNA noncoding, starvation up-regulated," because the abundance of rncs-1 was increased in response to starvation. The increase in rncs-1 abundance in response to starvation appeared to be mediated by an increase in transcription, as expression in the worms of green fluorescent protein (GFP) fused to the promoter region of rncs-1 showed a similar increase in abundance in response to starvation. In vitro assays for cleavage of rncs-1 by Dicer activity in embryo extracts showed that rncs-1 was not a substrate for Dicer, likely due to branched structures at the termini of the RNA. Instead rncs-1 inhibited the cleavage of Dicer target RNAs, decreasing the in vitro production of siRNAs. Furthermore, the expression of genes that are repressed by Dicer (through the production of small regulatory RNAs complementary to the target genes) was further decreased in worms deficient for rncs-1. The siRNAs targeting the mRNAs for these Dicer-regulated genes were decreased, while the mRNAs were increased in worms overexpressing rncs-1. The rncs-1-deficient animals failed to show a starvation or dauer phenotype, suggesting that rncs-1 is only a part of the response mechanism to food deprivation. Instead, in vivo overexpression of rncs-1 led to an increase in the frequency of males in the hermaphrodite population. The potential involvement of rncs-1 in sex determination is intriguing, as in other species, including mammals and flies, large noncoding RNAs are involved in X chromosome dosage compensation.

S. Hellwig, B. L. Bass, A starvation-induced noncoding RNA modulates expression of Dicer-regulated genes. Proc. Natl. Acad. Sci. U.S.A. 105, 12897-12902 (2008). [Abstract] [Full Text]

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