Introduction to special issue

In the Forests of RNA Dark Matter

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Science  02 Sep 2005:
Vol. 309, Issue 5740, pp. 1507
DOI: 10.1126/science.309.5740.1507

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For a long time, RNA has lived in the shadow of its more famous chemical cousin DNA and of the proteins that supposedly took over RNA's functions in the transition from the “RNA world” to the modern one. The shadow cast has been so deep that a whole universe (or so it seems) of RNA—predominantly of the noncoding variety—has remained hidden from view, until recently.

Nor is RNA quite so inert or structurally constrained as its cousin; its conformational versatility and catalytic abilities have been implicated at the very core of protein synthesis and possibly of RNA splicing. Noller (p. 1508) discusses how the basic building block of RNA—the double helix—has been fashioned into the intricate “protein-like” three-dimensional surfaces of the ribosome. A further parallel between RNA and protein is revealed in the structure of an RNA group I self-splicing intron, which uses an arrangement of two metal ions for phosphoryl transfer much like that seen in many protein enzymes (p. 1587). Another group I-like intron catalyzes the formation of a tiny RNA lariat, a reaction strikingly similar to one seen in group II introns and spliceosomal introns (pp. 1584 and 1530). This unusual lariat, at the very 5' end of the resultant mRNA, is suggested to help protect the mRNA from degradation. The dynamics of the RNA messages passed between nucleus and cytoplasm provide a complex and sophisticated layer of regulation to gene expression, covered by Moore (p. 1514), who describes the teams of proteins that escort and regulate mRNA throughout the various stages of its life (and death). Death for many mRNAs occurs in cytoplasmic foci called P-bodies, which can also act as temporary storage depots for nontranslating mRNAs (see the Science Express Report by M. Brengues et al.).

CREDIT: A. Baucom and H. Noller

Small noncoding microRNAs (miRNAs) have been found in such abundance that they have been christened the “dark matter” of the cell, a view reinforced by an analysis of the small RNAs found in Arabidopsis (pp. 1567 and 1525). The role of miRNAs and of their close cousins small interfering RNAs (siRNAs) in RNA silencing is discussed by Zamore and Haley (p. 1519), and illustrated in the poster pullout in this issue and in research showing that miRNAs can repress the initiation of translation (p. 1573) and, intriguingly, can also increase mRNA abundance (p. 1577). [See also this week's online Science of Aging Knowledge Environment (SAGE KE) and Signal Transduction Knowledge Environment (STKE)]. The phrase “dark matter” could well be ascribed to noncoding RNA in general. The discovery that much of the mammalian genome is transcribed, in some places without gaps (so-called transcriptional “forests”), shines a bright light on this embarrassing plentitude: an order of magnitude more transcripts than genes (pp. 1559, 1564, and 1529). Many of these noncoding RNAs (p. 1527) are conserved across species, yet their functions (if any) are largely unknown: A cell-based screen shows one, NRON, to be a regulator of the transcription factor NFAT (p. 1570). Of course, in some cases it is the act of transcription that is the regulatory event, as in the case of the transcriptional regulation of recombination (p. 1581). Finally, even the coding and base-paring capacity of RNA can be altered—by RNA editing, in which bases in the RNA are changed on the fly. Analysis of editing enzymes (p. 1534) reveals that the cell-signaling molecule IP6 is required for their editing activity.

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