New insights into short-chain prenyltransferases: structural features, evolutionary history and potential for selective inhibition

Isoprenoids form an extensive group of natural products involved in a number of important biological processes. Their biosynthesis proceeds through sequential 1′-4 condensations of isopentenyl diphosphate (C₅) with an allylic acceptor, the first of which is dimethylallyl diphosphate (C₅). The reactions leading to the production of geranyl diphosphate (C₁₀), farnesyl diphosphate (C₁₅) and geranylgeranyl diphosphate (C₂₀), which are the precursors of mono-, sesqui- and diterpenes, respectively, are catalyzed by a group of highly conserved enzymes known as short-chain isoprenyl diphosphate synthases, or prenyltransferases. In recent years, the sequences of many new prenyltransferases have become available, including those of several plant and animal geranyl diphosphate synthases, revealing novel mechanisms of product chain-length selectivity and an intricate evolutionary path from a putative common ancestor. Finally, there is considerable interest in designing inhibitors specific to short-chain prenyltransferases, for the purpose of developing new drugs or pesticides that target the isoprenoid biosynthetic pathway.     

Induction of developmental anomalies in mice by maternal stress

The short-time restraint of pregnant mice on day 8 of gestation led to a significant increase of the anomaly rate in fetuses. This effect may be due to stress factors of endocrine origin.     

Asteroseismology: oscillations on the star Procyon

Stars are spheres of hot gas whose interiors transmit acoustic waves very efficiently. Geologists learn about the interior structure of Earth by monitoring how seismic waves propagate through it and, in a similar way, the interior of a star can be probed using the periodic motions on the surface that arise from such waves. Matthews et al. claim that the star Procyon does not have acoustic surface oscillations of the strength predicted. However, we show here, using ground-based spectroscopy, that Procyon is oscillating, albeit with an amplitude that is only slightly greater than the noise level observed by Matthews et al. using spaced-based photometry.     

DNA damage defines sites of recurrent chromosomal translocations in B lymphocytes

Recurrent chromosomal translocations underlie both haematopoietic and solid tumours. Their origin has been ascribed to selection of random rearrangements, targeted DNA damage, or frequent nuclear interactions between translocation partners; however, the relative contribution of each of these elements has not been measured directly or on a large scale. Here we examine the role of nuclear architecture and frequency of DNA damage in the genesis of chromosomal translocations by measuring these parameters simultaneously in cultured mouse B lymphocytes. In the absence of recurrent DNA damage, translocations between Igh or Myc and all other genes are directly related to their contact frequency. Conversely, translocations associated with recurrent site-directed DNA damage are proportional to the rate of DNA break formation, as measured by replication protein A accumulation at the site of damage. Thus, non-targeted rearrangements reflect nuclear organization whereas DNA break formation governs the location and frequency of recurrent translocations, including those driving B-cell malignancies.     

Divergent effects of theophylline on adenylate cyclase preparations from guinea-pig heart and lung

Zusammenfassung Theophyllin verringert die Aktivität der Adenyl-Cyclase (AC) in der plasmamembranreichen Fraktion der Meerschweinchenlunge in Konzentrationen von 6–10 mM; es hat dagegen keinen Einfluss auf die Aktivität der AC in Meerschweinchenherzen. Diese Resultate weisen darauf hin, dass in verschiedenen Geweben geringe Unterschiede in der Enzym-Katalyse bestehen können.     

A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation.