Reviews & Analysis

Prion 'strains', multiple conformations of the same misfolded protein, have captured great interest because of their role in transmission of mad cow disease to humans. Prion strains have also been observed in yeast, where self-propagating protein folds are responsible for inheritable traits. Recent findings reveal an exciting new insight into the structural basis of this phenomenon.

A recent study using electron microscopy provides a detailed view of the oligomerization of a protein complex on the surface of a microtubule polymer. The findings point to a new type of interaction that may be well suited to couple the movement of cargo to dynamic cytoskeletal polymers.

Using a previously developed method, Singer and co-workers have now labeled RNA transcripts and quantitatively measured the synthesis of RNA in living cells. They find that only a small fraction of the RNA polymerases that bind the promoter actually produce messenger RNA. They also observed much faster elongation than previously reported, along with frequent long pauses.

Neurotransmitter:sodium symporters, which use sodium gradients for the coupled uptake of sodium and neurotransmitters during synaptic transmission, often display a chloride dependence. New data from two separate groups identify the chloride-binding site for this family of symporters and suggest that the chloride charge facilitates sodium binding and substrate transport.

Targeting of enzymes regulating chromatin organization to specific histone residues is a key element in the hugely complex system of epigenetic signaling that controls gene regulation and repair. Understanding of how targeting is achieved is still limited, but structures of the histone lysine demethylase JMJD2A in complex with substrate peptides now offer insight into its dual specificity.

Small RNAs can silence target genes by a variety of pathways and mechanisms. Specific microRNAs have now been shown to partition into distinct effector complexes, which may in turn affect their silencing output.

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.

The Protein Structure Initiative of the US National Institutes of Health has entered its second year. Its status is reported here, as discussed at December's meeting of the principal investigators.

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.