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CONTINUED FROM 1453 THIS WEEK IN Noncoding RNAs at Work One type of the small noncoding RNAs (ncRNAs), microRNAs (miRNAs), 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. (p. 1573, published online 4 August 2005) 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. (p. 1570) 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 though modulation of NFAT’s cellular localization. Trapped by an Editor A family of RNA editing enzymes, adenosine deaminases that act on RNA (ADARs), is important for proper neuronal function and are implicated in the regulation of RNA interference. Macbeth et al. (p. 1534) determined the crystal structure of human ADAR2 at 1.7 angstrom resolution. Surprisingly, inositol hexakisphosphate (IP 6 ) is buried within the fold of the enzyme core. Activity assays show that IP 6 is required for hADAR2 activity and for the activity of a yeast RNA editing enzyme, ADAT1. Small Takeover, Big Gain Viruses exploit host functions in many ways in order to replicate. Identified functions now include taking over host-encoded microRNAs (miRNAs) that play a crucial role in RNA interference, a recently discovered mechanism of gene regulation. Studying the human pathogen hepatitis C virus (HCV), Jopling et al. (p. 1577) show that a host miRNA that is abundantly expressed in the liver, where the virus replicates, interacts with the 5′ noncoding region of the viral RNA. This interaction leads to an increase in HCV RNA and possibly contributes to viral persistence in the liver. Inactivation of this miRNA could be a useful therapeutic strategy for HCV, which is estimated to affect 170 million people worldwide. CREDIT: MACBETH ET AL. Similarities in Splicing Group I self-splicing introns have been thought to be distinct from their group II cousins and messenger RNA (mRNA) splicing reactions in not generating a lariat (looped) intermediate that is subsequently removed from the spliced product. Nielsen et al. (p. 1584) show a group I−like ribozyme from the slime mold Didymium iridis also produces a lariat. The DiGIR1 ribozyme cleaves its RNA target to form a microlariat at the extreme 5′ end of its parent homing endonuclease mRNA. The lariat might function in an analogous manner to the cap found on regular polymerase II mRNAs. The evolution of the GIR1 ribozyme might parallel a possible step in the evolution of mRNA splicing. Biochemical studies of group 1 intron splicing have shown that both of its chemical steps require divalent metal ions, and several metal ligands have been identified. Mechanisms involving either two or three metal ions have been proposed. Stahley and Strobel (p. 1587) have determined the structure of an intron splicing intermediate that is active in catalyzing exon ligation. The active site contains two Mg 2+ ions that coordinate all six of the biochemically identified ligands. Thus, an RNA phosphotransferase can function through a twometal-ion mechanism. www.sciencemag.org SCIENCE VOL 309 2 SEPTEMBER 2005
What if moving from one particular protein to the most relevant journal and patent literature were as easy as pushing a button? It is. Not only does SciFinder provide access to more proteins and nucleic acids than any publicly available source, but they’re a single click away from their referencing patents and original research. Coverage includes everything from the U.S. National Library of Medicine’s (NLM) MEDLINE ® and much more. In fact, SciFinder is the only single source of patents and journals worldwide. Once you’ve found relevant literature, you can use SciFinder’s powerful refinement tools to focus on a specific research area, for example: biological studies such as target organisms or diseases; expression microarrays; or analytical studies such as immunoassays, fluorescence, or PCR analysis. From each reference, you can link to the electronic full text of the original paper or patent, plus use citation tools to track how the research has evolved and been applied. Visualization tools help you understand results at a glance. You can categorize topics and substances, identify relationships between areas of study, and see areas that haven’t been explored at all. Comprehensive, intuitive, seamless—SciFinder directs you. It’s part of the process. To find out more, call us at 1-800-753-4227 (North America) or 1-614-447-3700 (worldwide) or visit www.cas.org/SCIFINDER. Part of the process ṢM A division of the American Chemical Society. SciFinder is a registered trademark of the American Chemical Society. “Part of the process” is a service mark of the American Chemical Society.
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Page 33 and 34: New England Biolabs - an uncommon p
Page 35 and 36: N EWS OF THE W EEK SPACE-BASED ASTR
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Page 40 and 41: CVS and amniocentesis are 99% accur
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Page 45 and 46: Cosmology The Quest for Dark Energy
Page 47 and 48: The power of small. It’s a small
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RNA S PECIAL S ECTION REVIEW RNA St
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RNA S PECIAL S ECTION Ascribing fun
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RESEARCH ARTICLE Inositol Hexakisph
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R ESEARCH A RTICLE IP 6 is required
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R ESEARCH A RTICLE Fig. 6. (A) Edit
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R EPORTS SWNT allows for an easily
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R EPORTS Controlling the Kondo Effe
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R EPORTS system. Moreover, the crys
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R EPORTS cylindrical shells centere
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R EPORTS downhill currents is quite
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R EPORTS The long-term behavior of
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R EPORTS Our second method for esti
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R EPORTS realizations reduces noise
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R EPORTS large majority of transcri
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R EPORTS Fig. 3. Noncoding RNA prom
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R EPORTS Antisense Transcription in
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R EPORTS transcripts are processed
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R EPORTS Fig. 1. Small RNAs map to
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R EPORTS A Strategy for Probing the
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R EPORTS increase in NFAT activity
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R EPORTS ER-HA-RL expression was si
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R EPORTS ner. The simultaneous coor
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