News & Views in 2007

microRNAs (miRNAs) and small interfering RNAs from plants are 2′-O-methylated at their 3′ termini. Although miRNAs from animals are not methylated, two studies show that the recently identified mammalian Piwi-interacting RNAs carry a 2′-O-methyl group on the 3′ terminal ribose.

Karni et al. report in this issue that proteins in the SR family, which modify gene function by alternative splicing, are among the many factors that can transform mammalian cells to malignancy. These splicing proteins regulate alternative splicing of many known proto-oncogenes and tumor-suppressor genes, thereby activating them post-transcriptionally to allow cells to escape normal controls on cell growth and proliferation.

Analyses of telomere-binding proteins show structural and functional conservation with subunits of replication protein A, the canonical single-stranded DNA–binding protein. These studies raise intriguing questions about the structure and general role of DNA binding in telomere length homeostasis.

Recent structural and functional analyses of MthK, a prokaryotic Ca²⁺-activated K⁺ channel, suggest that the interplay between cytoplasmic Ca²⁺ and H⁺ concentrations determines the oligomeric stability of its associated RCK domain and thus controls activation gating. However, the discovery of a ligand-dependent desensitization process suggests that gating in these channels might be more complicated than originally envisioned.

RNA interference (RNAi) is important in directing heterochromatin assembly at centromeres in fission yeast, which is crucial for maintaining a stable genome through mitotic and meiotic divisions. In this issue, Buker et al. describe a new Argonaute siRNA chaperone (ARC) that converts duplex RNA to single-stranded RNA. This is a previously unknown step in the RNAi-directed heterochromatin-formation pathway.

A timely study in this issue reports the high-resolution crystal structure of the human plasma protein cholesteryl ester transfer protein (CETP) with its natural lipid ligands. The crystal structure will enhance both basic research on CETP-mediated cholesterol lipid transfer and the design of new drugs that increase plasma high density lipoprotein (HDL) cholesterol.

Selenocysteinyl-tRNA^Sec is used by many organisms from all three domains of life to incorporate selenocysteine (Sec) site-specifically into certain proteins. Two recent reports have identified a new Sec synthase that catalyzes the last step in the generation of this aminoacyl-tRNA in eukarya and archaea.

Histone lysine methylation has a central role in transcriptional regulation and has recently been linked to DNA damage repair. Now it has been shown that the DNA damage repair factor 53BP1 is recruited to DNA double-strand breaks by its tandem tudor domain, which specifically recognizes histone H4 dimethylated at lysine 20.

The central function of kinetochores is to grasp a dynamic microtubule. Structural, biochemical and cell biological approaches have converged to uncover a microtubule-binding activity within the Ndc80/HEC1 complex, providing a satisfying answer to a question that has puzzled biologists for the last century.

The exosome, the major eukaryotic 3′ exoribonuclease acting in processing or degradation of a wide variety of RNA substrates, contains six subunits with predicted phosphorolytic activity and a single hydrolytic subunit. Recent data suggest that the phosphorolytic subunits of the yeast enzyme are catalytically inactive, and the hydrolytic subunit is solely responsible for the activity of the core exosome.

The structures of APOBEC2 and TadA, members of a superfamily of Zn-dependent deaminases, reveal unexpected features and provide insight into the ability of some family members to act on DNA.

Two independent crystal structure analyses have resolved the detailed interactions between botulinum neurotoxin serotype B and its neuronal receptor, synaptotagmin. The studies show how the toxin binds synaptotagmin and, along with previously determined interactions with the ganglioside G_T1b, a coreceptor, explain the toxin's extreme toxicity and tropism for neurons.