Research articles

The authors perform a computational analysis of mutagenesis at non-B DNA structures formed by repetitive sequences. Having removed confounding factors, they present a landscape of mutagenesis different than previously thought, in which mechanisms such as the formation of abnormal secondary structures, polymerase slippage and occasional takeover by error-prone polymerases play an important role within, but not surrounding, the motifs.

Here the authors computationally test the hypothesis that RNA organizes the three-dimensional genome via a triplex-forming mechanism, providing evidence that lncRNA-targeted triplex hotspots can contribute to large-scale chromosome compartmentalization.

Analysis of 18 available structures and other data reveals a new, conserved structural motif in arrestins and suggests that different phosphorylation patterns of the GPCR C terminus can drive distinct arrestin conformations and functional outcomes.

Genome-wide analyses of somatic mutations across six cancer types show that mutation frequencies differ between chromosomal regions located at the nuclear core versus the periphery, and thus mutational patterns are influenced by nuclear architecture.

Comparative analysis of RNA-seq and ribosome profiling data show that a major fraction of exon-skipping events in transcripts with medium-to-high abundance are engaged by ribosomes and therefore are likely to be translated.

An analysis of previously published data on fiber formation by sickle-cell hemoglobin reveals a universal curve when delay time is plotted against supersaturation (ratio of protein concentration to solubility).

Analyses of yeast codon usage and ribosome profiling data reveal a nonoptimal codon cluster in the mRNAs of ER-targeted proteins, downstream of the SRP-binding site, that would slow down translation to promote SRP interaction.

A systematic analysis reveals features of proteins synthesized at distal locations owing to mRNA localization, including the presence of intrinsically disordered segments and assembly-promoting modules. These findings suggest that asymmetric protein distribution enhances interaction fidelity.

Rare or nonoptimal codons that cause ribosomes to pause have been suggested to be important determinants of cotranslational folding. A revised translational efficiency scale, which considers tRNA abundance as well as codon usage and codon-tRNA interaction, now suggests a correlation between optimal or nonoptimal codon usage and secondary structure of the nascent polypeptide.

A comprehensive metagenomic analysis of chromatin immunoprecipitation–sequencing and microarray analysis (ChIP-seq and ChIP-chip) data from mouse embryonic stem cells provides insight into how histone gene transcription is controlled. The work reveals a complex mode of regulation, with multiple factors acting to regulate transcription of core and linker histones.

The location of DNA breakpoints associated with somatic copy-number alterations in cancer genomes is analyzed, revealing an enrichment of sequences with propensity to adopt G-quadruplex conformation, often near transcription start sites, and a correlation with hypomethylation. The analysis indicates that G4 formation contributes to cancer genome instability.

A dataset of SNPs and indels from the human genome has now been compared to nucleosome occupancy profiles. Indels tend to be less represented around regions occupied by nucleosomes, whereas SNPs are enriched around nucleosomes in bulk but depleted relative to covalently modified histones, giving insight into genome organization and its possible link to variation.

Chromatin carries various modifications that have been related to DNA and RNA metabolism. Analysis of numerous histone modifications across the human genome now demonstrates that intronic and exonic regions are enriched with distinct modifications. Studies of two alternatively spliced genes suggest that exon definition, rather than splicing, may contribute to these patterns.

Splicing and transcription have been argued to be coupled, but the mechanisms behind this are unclear. Published data sets examining nucleosome positioning are now analyzed and show that exons tend to have higher nucleosome occupancy than introns. This may indicate why metazoan exons are ∼150 nucleotides, similar to the length of DNA on a nucleosome.

Chromatin influences transcription, but its effects on downstream processing have been less clear. Analyses of published high-throughput data examining nucleosomal positions in T cell and C. elegans genomes now indicates that intron-exon architecture is reflected in nucleosome occupancy.

Most known nucleotidyl-transfer enzymes use two metal ions for catalysis, but some enzymes use only one divalent cation in their active sites. A comparative analysis of previously available structural data reveals that the one-metal-ion enzymes use a similar mechanism to coordinate their single metal ion, which corresponds, functionally and structurally, to metal ion B in the two-metal-ion enzymes.

The ATPase activity of AAA+ proteins is regulated by their interaction with ligands, but depending on the particular protein it can be stimulated or inhibited, and the mechanism for such control remained unclear. An analysis of previous structural data on various AAA+ proteins now reveals that a conserved glutamate residue adopts two conformations and and thus regulates the ATPase activity.