RNA world

A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon. Soifer, H. S. et al. Nucleic Acids Res. 33, 846–856 (2005)

Vigilins bind to promiscuously A-to-I-edited RNAs and are involved in the formation of heterochromatin. Wang, Q. et al. Curr. Biol. 15, 384–391 (2005)

These papers provide new insights into cellular responses to double-stranded RNA (dsRNA). LINE-1 elements pose a threat to genome integrity in human cells through their ability to move around by retrotransposition. Soifer et al. present the first evidence that LINE-1 dsRNAs are targets of the RNAi machinery, indicating that this pathway is one form of defence that the human genome uses against retrotransposition. dsRNAs from various sources also undergo promiscuous adenosine-to-inosine editing, and Wang et al. provide evidence that this leads to the formation of silent heterochromatin at the corresponding genomic sequences. RNAi and RNA editing therefore provide alternative and perhaps overlapping pathways to RNA-mediated silencing.

Technology

MAGIC, an in vivo genetic method for the rapid construction of recombinant DNA molecules. Li, M. Z. & Elledge, S. J. Nature Genet. 37, 311–119 (2005)

Conventional cloning is an expensive and time-consuming process that involves multiple steps from the initial DNA plasmid preparation to transformation. The need to achieve high-throughput recombinant-DNA production led Li and Elledge to design a new cloning method that involves only three steps. The approach relies on bacterial conjugation, in vivo site-specific endonuclease cleavage and homologous recombination to place the DNA fragment of interest under the control of new regulatory elements in the desired vector. It's cheap and easy — it's MAGIC.

Technology

Ubiquitous GFP expression in transgenic chickens using a lentiviral vector. Chapman, S. C. et al. Development 132, 935–940 (2005)

Production of transgenic chickens is an attractive goal for both pharmaceutical and developmental biologists, but has been held back owing to technical challenges. Chapman and colleagues now show that ubiquitous GFP expression in the chicken embryo can be achieved using a lentiviral vector. With the chicken genome sequence now available, this method will be useful for investigating gene expression during embryonic development — an important tool given that the chicken is an established developmental model. It also provides a model for a new generation of transgenics for studying the expression of pharmaceutical products in egg albumen.

Developmental genetics

Genetic programs activated by proneural proteins in the developing Drosophila PNS. Reeves, N. & Posakony, J. W. Dev. Cell 8, 413–425 (2005)

As their name suggests, proneural transcription factors promote neurogenesis. Their role is well established, unlike their mode of action, because few of their targets are known. Using whole-genome microarray analysis and in situ hybridization in proneural cell clusters, the authors identified a set of genes that are preferentially expressed in these cells. Loss of function of two of the candidates confirmed their role in PNS development. Sequence analysis and reporter studies allowed the authors to describe cis-regulatory elements that direct proneural gene expression.

Evolution

Sex peptide causes mating costs in female Drosophila melanogaster. Wigby, S. & Chapman, T. Curr. Biol. 15, 316–321 (2005)

Male fruitflies pass a cocktail of accessory-gland proteins (Acps) to females during mating. Not only do these elicit a range of post-mating behavioural changes in females, but they are toxic, reducing female survival and reproductive success. Chapman and Wigby found that a single Acp — the sex peptide — is responsible for most of this cost of mating, making the sex peptide, which also stimulates egg production and reduces female sexual receptivity, the first identified protein that is likely to have a role in sexual conflict.

Human disease

Inactivation of TGFBβ signaling in neural crest stem cells leads to multiple defects reminiscent of DiGeorge syndrome. Wurdak, H. et al. Genes Dev. 19, 530–535 (2005)

This paper provides a link between transforming growth factor-β (TGFB) signalling and DiGeorge syndrome, which is typically associated with a small deletion of human chromosome 22. Mice that were engineered to lack the TGFB receptor in neural crest cells showed many features of DiGeorge syndrome. The chromosome 22 micro-deletion does not remove any members of the TGFB pathway, but it contains a gene, CrkL, that interacts with TGFB signalling.

Functional genomics

A universal plasmid library encoding all permutations of small interfering RNA. Chen, M. et al. Proc. Natl Acad. Sci. USA 102, 2356–2361 (2005)

Small interfering RNA (siRNA) libraries are limited to targeting predicted or known genes, restricting their usefulness in species for which the transcriptome is uncharacterized. Chen et al. circumvented this problem by constructing a library of 5 × 107 plasmids containing all permutations of siRNA sequences. The library should enable large-scale RNAi screens to be carried out in any organism or cell type.