Volume 21 Issue 6, June 2014

X-ray structural analysis of spliceosomal U6 small nuclear RNA bound to Prp24 reveals a complex interlocked RNA–protein assembly and suggests models for key steps in spliceosome assembly and recycling.

New high-resolution structures of microtubules reveal that GTP and taxol each stimulate microtubule assembly by inducing straight protofilaments and promoting extension of the interdimer spacing. However, these effects take place through different mechanisms: GTP directly extends loops around the active site, whereas taxol works like a remote lever.

The enzyme telomerase consists of a reverse transcriptase (TERT) bound to a telomerase RNA (TR) component. Now, the first cocrystal structure of vertebrate telomerase core RNA and protein domains reveals new RNA-protein interactions central to formation of a catalytically active RNP.

Autophagy initiates with the assembly of a preautophagosomal structure (PAS), triggered by the yeast Atg1 complex. Ohsumi, Noda and colleagues present the crystal structures of Atg13–Atg1 and Atg13–Atg17, revealing how starvation-induced dephosphorylation of Atg13 triggers formationof the Atg1 complex and PAS assembly.

Tumor suppressor PTEN negatively regulates PI3K-AKT signaling by dephosphorylating PIP3. PTEN can also dephosphorylate peptide substrates in vitro, but the physiological relevance of this activity was unclear. Jiang and colleagues show that PTEN is a protein tyrosine phosphatase that selectively dephosphorylates insulin receptor substrate-1 and thus regulates cell metabolism and growth.

The CRISPR–Cas system mediates immunity to foreign DNA sequences that are integrated as spacers between repeats in the CRISPR locus. Work from Doudna and colleagues shows that nucleases Cas1 and Cas2 form a stable complex that recognizes the CRISPR leader-repeat sequence, thus determining the site of integration.

Tumor suppressor p53 can activate BAX or BAK; this activity is opposed by antiapoptotic protein BCL-xL, which sequesters p53. Now Kriwacki, Green and colleagues characterize the human p53–BCL-xL complex by NMR spectroscopy, thus allowing mutagenesis analyses to dissect p53's nuclear and cytosolic functions and BCL-xL's antiapoptotic mechanisms.

During spliceosome assembly, U6 snRNA is recycled from U2 snRNA by the protein Prp24 and is paired with U4 snRNA to form a splicing-competent complex. A structure of yeast Prp24 bound to the conserved core of U6 RNA reveals a new arrangement of RNA-protein contacts that mediates these early events leading to pre-mRNA splicing.

Proudfoot, Gullerova and colleagues show that mammalian Dicer localizes to the nucleus, where its levels are tightly regulated. Dicer interacts with RNA polymerase II and seems to restrict double-stranded (ds) RNA formation from convergent transcription. Dicer knockdown leads to accumulation of dsRNA, triggering the interferon response pathway and cellular apoptosis.

Condensins organize chromosomes to allow proper segregation during mitosis or meiosis. Haering and colleagues show that the two HEAT-repeat subunits of the condensin complex, Ycg1 and Ycs4, bind DNA; this interaction stimulates ATPase activity of the SMC subunits and is required for condensin association with chromosomes.

PRC2 promotes methylation of H3K27, a modification that recruits PRC1, which in turn deposits H2A ubiquitin marks. Müller and colleagues use biochemistry approaches to show that H2Aub recruits Jarid–Aebp2–containing PRC2 to promote H3K27 trimethylation on H2Aub nucleosomes, thus forming a positive feedback loop to establish repressed chromatin domains.