Reviews & Analysis

Glutamate transporters in neuronal membranes are also known to catalyze a 'leak' of chloride ions, for unknown biological purposes. Now a glutamate transporter homolog from evolutionarily distant microorganisms has been shown to contain a similar chloride leak.

The yeast proteins Sro7 and Sro77, and their metazoan relatives Lgl and tomosyn, interact with plasma membrane SNARE proteins and control cell polarity. Recently, the crystal structure of yeast Sro7 has been solved, yielding fascinating insights and even more unanswered questions concerning the molecular mechanism of these proteins.

Proper establishment, maintenance and removal of covalent post-translational modifications on histones are essential for normal cell physiology. In this issue, Nicolas et al. describe the characterization of two physically and functionally distinct Clr6 (Rpd3)-containing histone deacetylase complexes in fission yeast and implicate their activity in a number of processes, including transcriptional regulation, silencing and genomic integrity.

A recent report looks at a 'clock in a test tube' composed of the cyanobacterial proteins KaiA, KaiB and KaiC, revealing that these dancing proteins swap partners to keep track of time.

Sparked by the discovery of LSD1, the first bona fide histone lysine demethylase, a burst of research has opened a new era in understanding how chromatin is regulated, including the identification of the JmjC domain–containing histone demethylases. Now, several independent studies provide evidence that yeast Yjr119Cp, human JARID1 and Drosophila Lid, all members of the JmjC family, demethylate histone H3 trimethyl-Lys4, a mark of transcriptionally active chromatin.

Two new crystal structures shed light on how a component of the endosomal budding machinery is co-opted by human immunodeficiency virus-1 to facilitate virus budding from the cell surface.

In this issue, Nöllmann and colleagues report single-molecule analyses of DNA gyrase action on supercoiled DNA under different levels of strain. Surprisingly, they found that gyrase changes its reaction mechanism in response to changes in DNA strain. This explains the role of ATP in a branching topoisomerase reaction pathway and revisits an old puzzle about gyrase reversibility.

The functional assembly of a ciliate telomerase requires ordered RNA conformational changes mediated by a La motif–containing protein. This raises new questions about telomerase biogenesis and the evolutionary origin of the telomerase RNA.

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.