Articles in 2009

Escherichia coli YiiP, a member of the cation diffusion facilitator family, exports cytoplasmic zinc, maintaining cellular homeostasis. The high-resolution crystal structure of YiiP, combined with functional studies focused on its cytoplasmic C-terminal domain, suggest how it is able to allosterically modulate zinc transport.

The positions of nucleosomes can affect processes occurring on DNA. DNA curtains are now used to study nucleosome positioning in vitro. This allows assessment of sequence-related effects on positioning and indicates that the yeast factor Scm3 can overcome the aversion of nucleosomes to AT-rich sequences.

Nucleosomes can be modified by replacing the core histones with variants, the most diverse of which is macroH2A. The localization of macroH2A variants in human male pluripotent cells indicates that this variant functions in repression of key developmental genes and is essential for zebrafish embryogenesis.

An important aspect of eukaryotic gene expression is the efficient integration of transcription, pre-mRNA processing and nuclear export. A new study demonstrates that pre-mRNA transcript continuity is an essential component for maintaining productive coupling of transcription and RNA processing events.

The adequate and on-time response of cellular transcription to internal needs and external stimuli is a delicate task. Is the transcriptional regulator p53 on call to permit rapid activation of its target genes? A new study reports interplay of p53 with a previously unidentified regulator, calcineurin-binding protein 1 (Cabin1), and provides evidence for such a mechanism.

Manuscript peer reviewing is at the heart of the scientific system, but it seems that these duties are often not properly (if at all) recognized by universities, funding agencies or even the rest of the scientific community.

Using bioinformatics analysis of previously published global genome deep-sequencing data, two papers now show that DNA sequences associated with nucleosomes are preferentially located in exons. The correlation between nucleosome distribution and the exon-intron organization of genes may have a key role in exon recognition at the pre-mRNA level during co-transcriptional splicing, consistent with previous findings indicating chromatin-mediated regulation of alternative splicing.

Macrodomains function as binding modules for metabolites of NAD⁺, including poly(ADP-ribose). Three new studies explore how binding of poly(ADP-ribose) by the macrodomains of histone variant macroH2A1.1 and the ATP-dependent chromatin-remodeling protein ALC1 (also called CHD1L) leads to the modulation of chromatin structure, regulating nuclear functions such as DNA-damage detection and repair.

DNA polymerase δ (Pol δ) has a crucial role in eukaryotic replication. Now the crystal structure of the yeast DNA Pol δ catalytic subunit in complex with template primer and incoming nucleotide is presented at 2.0-Å resolution, providing insight into its high fidelity and a framework to understand the effects of mutations involved in tumorigenesis.

The let-7 microRNA has been implicated in development and disease. Its expression must thus be tightly regulated, and previously uridylation and Lin28 were implicated in let-7 stability. Zcchc11 is now shown to be the uridylase that mediates pre–let-7 modification and regulates mature let-7 levels and activity in mouse embryonic stem cells.

Developmental expression of the microRNA let-7 is tightly regulated in many animals, and turnover has been linked to LIN-28 and uridylation in mammals. This regulation is now shown to be conserved in Caenorhabditis elegans, and PUP-2 is shown to be a uridylase that is specifically recruited to let-7 in a LIN-28–dependent manner.

Nucleosomes can interfere with DNA binding by factors, but previous work showed that protein-binding sites on a single nucleosome are accessible. Dynamics in the context of higher-order chromatin structure are now examined, with compaction dynamics and DNA-binding site exposure on a centrally placed nucleosome in an array assessed.

Co-transcriptional splicing of pre-mRNAs has been proposed to involve exon tethering to the elongating RNA polymerase II. By inserting a fast-cleaving ribozyme in the nascent transcript, the linear integrity of the transcript is found to be key to splicing, arguing against tethering and for a pathway that clears such disrupted transcripts.

X family DNA polymerases can fill short DNA gaps by binding both the 5′ and 3′ ends of the gap. What happens to the template strand is now revealed in the crystal structure of human polymerase λ bound to a 2-nucleotide gap substrate. The template strand is scrunched, with the additional base in an extrahelical position going into an enzyme pocket.

Prions can adopt a transmissible β-sheet-rich conformation and also form strains with different structural and biological properties. Polymorphic crystal structures of peptides from prion- and other amyloid-forming proteins suggest the structural basis for prion strains, revealing two potential mechanisms: packing and segmental polymorphism.

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.

miRNAs are loaded onto Argonautes (Agos) to guide silencing of targets, but duplex unwinding is required for targeting. Detection of Drosophila Ago1 complexes containing the duplexed or unwound miRNA now give insight into the basis for cleavage-independent unwinding of miRNA duplexes to generate a functional, mature complex.

Phosphorylation-dependent SUMOylation of MEF2A promotes postsynaptic dendrite differentiation. Analyses now reveal that a surface on the SUMO E2 UBC9 is responsible for integrating phosphorylation signal recognition and SUMOylation and suggests that regulation of some SUMO substrate recognition events may have evolved to use the E2 rather than an E3 ligase.

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.