Articles in 2014

Type I CRISPR-Cas systems require a target-searching Cascade complex and the Cas3 degradation machine to drive prokaryotic adaptation to alien nucleic acids. Cas3 crystal structures now reveal the mechanism of concerted DNA unwinding and degradation.

Replication of Nipah virus, which causes human encephalitis, requires delivery of viral nucleoprotein N to the viral genome by phosphoprotein chaperone, P. The crystal structure of the N⁰–P core complex now reveals how the chaperone prevents premature N assembly on RNA and identifies a potential target for antiviral drugs.

The protein Cereblon, part of an ubiquitin E3 ligase complex, is the target for anticancer thalidomide analogs. The crystal structure of human Cereblon-DDB1 with bound lenalidomide reveals how the drug affects E3 substrate recruitment.

A combination of fluorescence and cross-linking assays are used to elucidate the reciprocal effects of RNA polymerase pausing and the secondary structure of the nascent transcript as it emerges from the translocating enzyme's RNA-exit channel.

EF-G catalyzes translocation of tRNA–mRNA in the ribosome. Biochemical and structural analyses of EF-G indicate that EF-G disrupts interactions between the decoding center and the codon–anticodon duplex that constitute the barrier for translocation.

The development of new strategies to deplete maternal histone proteins in vivo and in vitro has led to the discovery of unexpected roles of histones in forming a functional nuclear envelope.

Classical PUF proteins bind to single-stranded RNA with sequence specificity that can be engineered by site-directed mutagenesis according to a simple RNA-recognition code. Now in-depth probing of the PUF RNA-recognition code enhances future design of PUF proteins and exposes hidden complexity in generating specificity.

Mechanisms of DNA damage repair within actively transcribed genes are poorly understood. Five new reports shed light on the contributions of chromatin to this process by uncovering roles for histone H3 Lys36 methylation, a post-translational modification previously linked to transcription elongation, in the control of DNA-damage signaling and double strand break repair.

The precursor for miRNA-151 is found to compete with mature forms for target sites on E2f6 mRNA but not on a different mRNA. These findings indicate that miRNA processing can affect individual mRNA targets differently.

Eukaryotic initiation factor 5b (eIF5B) is essential for translation initiation. Spahn and colleagues now report cryo-EM structures of the mammalian 80S initiation complex associated with eIF5B that redefine eIF5B as a tRNA reorientation factor.

Guettou et al. describe structural studies on a bacterial homolog of PepT1 and PepT2 peptide transporters—nutrient transporters responsible for all peptide transport across the plasma membrane—in complex with three di- or tripeptides. The data suggest how the transporter's broad peptide specificity is achieved.

MAP kinases recognize pathway-specific substrates via docking interactions. NMR analyses now reveal that docking interactions also stimulate ATP binding and phosphotransfer activity of p38α via an allosteric mechanism.

A screen identifies 15 genes that modulate CUG-repeat toxicity in C. elegans, including those encoding RNA-export and clearance factors. Toxic RNAs are recognized by the NMD pathway via their 3' UTR GC content.

Structural elucidation of the RNA aptamer 'Spinach' reveals that a new G-quadruplex structure forms the fluorophore-binding site that confers the ability of the RNA to function as a GFP mimic.

Roquin controls T-cell activity through interactions with mRNAs of stimulatory receptors. Structural and functional elucidation of its RNA-binding domain reveals how it interacts with constitutive decay elements in the 3' UTR of its targets to regulate their expression.

Roquin recognizes the CDE element in mRNAs to promote their decay. Crystal structures of human Roquin ROQ domain in complex with RNA reveals two distinct RNA-binding sites for stem-loop RNA and dsRNA.

Two sibling DNA polymerases synthesize most of the eukaryotic nuclear genome. A new study provides insights into the distinct protein interactions that deliver these replicases for asymmetric leading- and lagging-strand replication and reveals possible cross-talk between DNA replication and other cellular processes.

Eukaryotic DNA replication is carried out by two DNA polymerases, Pol ɛ and Pol δ. An in vitro–replication system reconstituted with purified yeast components identifies the factors that selectively recruit each polymerase for leading- or lagging-strand synthesis.

Mammalian RPRD proteins bind the phosphorylated CTD of RNA pol II with different affinities. Structural elucidation and characterization of their CTD interaction domains reveal the basis of RPRD binding preferences and a role in directing CTD dephosphorylation.

Post-transcriptional mRNA regulation is often attained by lengthening or shortening the 3′ poly(A) tail of a transcript. Eukaryotic mRNAs show a spectrum of deadenylation rates, thus allowing intricate control of gene expression, but the mechanisms that determine such rates are unclear. Three new studies highlight the structural and biochemical features of a key enzyme in removing poly(A) tails, the PAN2–PAN3 complex, providing clues to how different mRNA deadenylation rates can be achieved.