Ageing

Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Mostoslavsky, R. et al. Cell 124, 315–329 (2006)

The yeast Sir2 protein regulates DNA recombination and, thereby, ageing in budding yeast. Knockout of the mammalian Sir2 homologue Sirt6 results in mice with ageing-related, degenerative pathologies, and genomic instability that is caused by defective base-excision repair. The mice also suffer from metabolic abnormalities. So, although there are functional analogies between SIRT6 and Sir2, the pathways that are affected by their deficiency seem to differ.

Technology

In vivo identification of ribonucleoprotein–RNA interactions. Zielinski, J. et al. Proc. Natl Acad. Sci. USA 103, 1557–1562 (2006)

The authors developed a method for the in vivo identification of protein–RNA interactions by using a stable nucleic-acid homologue, peptide nucleic acid (PNA). PNA oligomers were linked to a peptide that can cross the extracellular-membrane lipid bilayer to ensure the efficient delivery of the compound into living cells. PNA hybridizes to its complementary mRNA target, and can subsequently be activated by ultraviolet irradiation, which causes it to crosslink to nearby RNA-binding proteins.

Development

Developmental control of nuclear morphogenesis and anchoring by charleston , identified in a functional genomic screen of Drosophila cellularisation. Pilot, F. et al. Development 133, 711–723 (2006)

Developmental control of nuclear size and shape by kugelkern and kurzkern. Brandt, A. et al. Curr. Biol. 1 Feb 2006 (10.1016/j.cub.2006.01.051)

Two groups have identified a novel nuclear envelope protein, Charleston/Kugelkern, that contains a farnesylation site, which is required for its anchorage to the inner nuclear membrane. Nuclear-envelope-associated Charleston/Kugelkern helps regulate the size, shape and position of nuclei in the Drosophila melanogaster embryo.

Small RNAs

Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Duchaine, T. F. et al. Cell 124, 343–354 (2006)

The Dicer enzyme can process double-stranded RNA into small RNAs that initiate different gene-silencing mechanisms. Duchaine and colleagues used a proteomics approach to identify proteins that interacted with the Caenorhabditis elegans Dicer DCR-1. By characterizing deletion alleles of the 20 interacting proteins, 12 were linked to the function of DCR-1 or its small-RNA products. The RNA phosphatase homologue PIR-1 and the Dicer-related helicase DRH-2 are required for RNA interference, whereas four other proteins are needed for the accumulation of several endogenous small RNAs. These findings imply that Dicer requires pathway-specific factors.