This Week in Science

Science  27 Nov 2009:
Vol. 326, Issue 5957, pp. 1159
  1. Revealing the RNA World?


      The RNA World hypothesis posits that at an early step in the appearance of life, RNA acted both as an information storage molecule and as an enzyme—or ribozyme. Such dual functionality would allow for an RNA species that could replicate itself and thus seed the beginning of molecular evolution. The involvement of RNA in a number of fundamental cell biological processes, together with its ability, either naturally or through in vitro evolution, to catalyze a range of chemical reactions, provides some indirect support for this view. Shechner et al. (p. 1271) have now determined the structure of an in vitro–evolved RNA ligase ribozyme that catalyses a chemical reaction essentially identical to that of proteins that replicate RNA. The active site of the RNA ligase could be superimposed upon that of the protein enzyme to reveal analogous residues important for the catalytic joining of RNA moieties. These findings will help in the engineering of more effective ribozyme polymerases.

    1. “Haploid Human”

        Genetic screens can provide direct insight into biological processes that are poorly understood. Carette et al. (p. 1231) describe genetic screens using large-scale gene disruption in human cells haploid for all chromosomes except for chromosome 8. One screen was used to identify host factors essential for the activity of cytolethal distending toxin, a toxin found in several pathogenic bacteria. Another screen identified host gene products essential for infection with influenza, and an additional screen revealed genes required for the action of adenosine 5′-diphosphate (ADP)–ribosylating bacterial toxins. This loss-of-function genetic approach in mammalian cells will be widely applicable to study a variety of biological processes and cellular functions.

      1. Simply Mycoplasma

          The bacterium Mycoplasma pneumoniae, a human pathogen, has a genome of reduced size and is one of the simplest organisms that can reproduce outside of host cells. As such, it represents an excellent model organism in which to attempt a systems-level understanding of its biological organization. Now three papers provide a comprehensive and quantitative analysis of the proteome, the metabolic network, and the transcriptome of M. pneumoniae (see the Perspective by Ochman and Raghavan). Anticipating what might be possible in the future for more complex organisms, Kühner et al. (p. 1235) combine analysis of protein interactions by mass spectrometry with extensive structural information on M. pneumoniae proteins to reveal how proteins work together as molecular machines and map their organization within the cell by electron tomography. The manageable genome size of M. pneumoniae allowed Yus et al. (p. 1263) to map the metabolic network of the organism manually and validate it experimentally. Analysis of the network aided development of a minimal medium in which the bacterium could be cultured. Finally, Güell et al. (p. 1268) applied state-of-the-art sequencing techniques to reveal that this “simple” organism makes extensive use of noncoding RNAs and has exon- and intron-like structure within transcriptional operons that allows complex gene regulation resembling that of eukaryotes.

        1. Crystal Growing Kit

            CREDIT: LI ET AL.

            For single crystals to remain intact, there is a limit to the size and number of defects that can be included before the underlying lattice is destroyed. Biological crystals, however, are known to include large macromolecules. H. Li et al. (p. 1244; see the Perspective by Hollingsworth) used electron tomography to study the crystallization of calcium carbonate inside an agarose gel, observing that the crystals physically entrapped the agarose macromolecules. To accommodate the curvature induced by the polymer chains, both high- and low-energy facets formed at the fiber-crystal interfaces. Thus, physical interactions alone may be sufficient for the incorporation of macromolecules in biological crystals and it may be possible to grow unusually shaped single crystals.

          1. Moving Cold Atoms with Quantum Ratchets

              The nanoscale dimensions of biological motors make them susceptible to thermal noise, but such motors can produce force in one direction by alternating application of an asymmetric potential, or ratchet, with periods of thermal drift in the motion. The quantum version of such motors can operate without dissipation, as long as there is some means to break time-reversal symmetry in the system. Salger et al. (p. 1241) report on a coherent quantum ratchet device consisting of Bose-Einstein condensate cold atoms placed into an asymmetric sawtooth-potential created by optical lattices. Symmetry breaking was accomplished by phase shifts in the driving potentials. As expected for such a quantum ratchet, the current depended on the initial phase of the driving potential.

            1. Cooperative Reduction

                Selective redox transformation remains a general challenge in chemical synthesis. All too often, the most readily available precursor to a compound must be over-reduced (or over-oxidized) and then carefully coaxed back to a desired intermediate state. Such is the case with the synthesis of cyclohexanone, which is mass-produced for use in the preparation of nylon: Access by direct reduction of phenol is plagued by the rapid addition of too many hydrogen atoms to the substrate, producing an alcohol (cyclohexanol) in place of the ketone. Liu et al. (p. 1250) have discovered that the unexpected cooperation of supported palladium and a Lewis acid such as aluminum trichloride—two catalysts widely used alone but rarely in concert—facilitates highly selective conversion of phenol to cyclohexanone near room temperature. The key appears to be inhibition of the undesired ketone-to-alcohol reduction step by the Lewis acid.

              1. Untangling the Web

                  Chlorophyll-containing phytoplankton is at the core of the marine food web. Martinez et al. (p. 1253) combined satellite data about upper ocean chlorophyll and sea surface temperatures to demonstrate a clear connection between phytoplankton and sea surface temperatures on a multidecadal time scale. Basin-scale ocean dynamic processes such as the Pacific Decadal Oscillation and the Atlantic Multidecadal Oscillation connect the physical, climate-related variability to changes in phytoplankton distribution and amount. Thus, improving the reliability of forecasts of large-scale ocean dynamics may help to improve predictions of changes in ocean community ecology.

                1. Patterns of Change

                    The global climate record of the past 1500 years shows two long intervals of anomalous temperatures before the obvious anthropogenic warming of the 20th century: the warm Medieval Climate Anomaly between roughly 950 and 1250 A.D. and the Little Ice Age between around 1400 and 1700 A.D. It has become increasingly clear in recent years, however, that climate changes inevitably involve a complex pattern of regional changes, whose inhomogeneities contain valuable insights into the mechanisms that cause them. Mann et al. (p. 1256) analyzed proxy records of climate since 500 A.D. and compared their global patterns with model reconstructions. The results identify the large-scale processes—like El Niño and the North Atlantic Oscillation—that can account for the observations and suggest that dynamic responses to variable radiative forcing were their primary causes.

                  1. RSV in 3D

                      CREDIT: TAWAR ET AL.

                      Respiratory syncytial virus (RSV) causes pneumonia and bronchiolitis in infants. RSV is an RNA virus in which the genomic RNA forms part of a nuclease-resistant helical ribonucleoprotein complex. Tawar et al. (p. 1279) now use x-ray and electron microscopy data to model the structure of this nucleocapsid complex and show how it can template RNA synthesis. The crystal structure shows RNA wrapped around a decameric ring of nucleocapsid protein. Combining this structure with electron microscopy data gives a model that shows how polymerase might read out the RNA bases without disassembling the nucleocapsid helix.

                    1. Inserting Introns

                        Introns—noncoding regions that interrupt coding gene sequences—are widespread throughout eukaryotic genomes, but intron gains and losses within and among species have been assumed to be rare. However, W. Li et al. (p. 1260) suggest that intron insertions can be relatively frequent within a population or species. By examining intron polymorphisms within genomes of different accessions of Daphnia pulpex (the water flea), and comparisons within the genus Daphnia, several instances of recent intron gains were observed, which appear to have occurred multiple times at the same site. Because intron insertions tend to be flanked by repetitive sequences, they may be the result of DNA damage repair mechanisms.

                      1. Pre-MicroRNA Export Machinery

                          Micro (mi) RNAs play a role in the regulation of many biological processes. Long transcripts are initially processed in the nucleus to yield pre-miRNAs that are translocated through the nuclear pore complex and further processed to mature miRNAs in the cytoplasm. Okada et al. (p. 1275; see the Perspective by Stewart) describe the crystal structure of pre-miRNA complexed with the exportin Exp5 and the small nuclear GTPase RanGTP. The structure shows that Exp5 and RanGTP protect the miRNA from degradation by nucleases, as well as facilitate transport to the cytoplasm. RNA recognition is mainly through ionic interactions that are sequence independent, and model-building suggests that this nuclear export machinery could accommodate other small-structured RNAs.

                        1. Sharp Nanowires

                            The potential for using nanowires in devices can be limited by the ability to synthesize them from two or more materials while maintaining compositional purity at the interfaces. Instead of using liquid droplets at the eutectic point when the melting point is at a minimum, Wen et al. (p. 1247) show that generating the wires at solid alloy catalysts allows fabrication of silicon germanium wires with atomically sharp interfaces. The system works well because an AlAu alloy composition was chosen in which Si and Ge have a low solubility but which have a high enough eutectic temperature so that nanowire growth is not limited by the reactivity of the Si and Ge precursors.

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