News & Views in 2007

How does RNA polymerase II cooperate with initiation factors to locate transcription start sites throughout the genome? A new cross-linking approach reveals previously unknown initiation factor–binding sites on the polymerase surface. The resulting model of the transcription initiation complex suggests that initiation factors cooperate above and inside the polymerase active center cleft to open DNA and find the transcription start site.

A new study reveals that cells naturally switch from expressing one polypyrimidine tract–binding protein (PTB) to a highly similar family member, nPTB, during the development of neurons, and shows that PTB itself regulates this transition. Ensembles of coregulated exons simultaneously change their splicing patterns, suggesting that this phenomenon could potentially mediate widespread changes in proteins composed of modular functional domains, thus driving neuronal phenotypes or disfavoring non-neuronal ones.

A study in this issue implicates SUMOylation of telomere-binding proteins by the SMC5/6 complex in alternative lengthening of telomeres.

MicroRNAs are small, noncoding RNAs that regulate gene expression in eukaryotes. The multipurpose protein hnRNP A1, a well-known factor in the regulation of precursor messenger RNA splicing, has now been implicated in the biogenesis of the microRNA miR-18a, shedding further light on the emerging topic of post-transcriptional regulation of microRNA expression.

The spliceosome, the ribonucleoprotein complex that removes introns from precursor messenger RNAs, is thought to undergo conformational changes between two alternative states to catalyze the two steps of the splicing reaction, a model that resembles ribosomal transfer RNA decoding. Following very different strategies, two papers provide new insights into how core components of the spliceosome and regulatory factors containing arginine/serine-rich domains with RNA chaperone activity can facilitate these conformational changes.

Cooperation between the DNA recombinase RAD51 and the breast cancer susceptibility protein BRCA2 is crucial for the repair of double-strand DNA breaks. Two papers provide new insight into the BRCA2-RAD51 interaction, revealing two different sets of motifs within BRCA2 that bind structurally distinct forms of RAD51. The balance between these interactions seems to be crucial for the function of BRCA2 in DNA repair.

Wnt signaling has key roles in embryogenesis and oncogenesis, yet several aspects of Wnt signal transduction remain mysterious. Schwarz-Romond et al. demonstrate that the Wnt signaling protein Dishevelled has the surprising ability to form dynamic polymers and present evidence that polymerization is crucial in signaling, perhaps forming an inducible scaffold for further signal transduction.

The solution structures of multiple forms of the adaptor protein CRK show how its domains fit together, providing insight into the autoregulation and ligand-mediated regulation of CRK.

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.