Browse Articles

Maintenance of genome integrity, cell division and gene expression have all been shown to be regulated by the condensation of DNA into heterochromatin. In a study published in this issue, Bulut-Karslioglu et al. reveal a new heterochromatin function for transcription factors in a mammalian system. They show that instead of activating gene expression, in the context of heterochromatic repeats, specific transcription factors are necessary for the maintenance of transcriptional repression and heterochromatin.

The recently solved crystal structure of the procollagen C propeptide reveals the basis for chain selectivity as well as an unexpected asymmetry to this homotrimeric molecule. In addition, mapping disease-causing mutations to the structure demonstrates clear correlation between severity of disease and mutation location.

SecY and Sec61 translocons mediate the orderly insertion of transmembrane segments into the lipid bilayer during membrane-protein biogenesis. Reporting in this issue, Ismail et al. now use a SecM-based molecular force sensor to show that the translocon exerts a pulling force on the nascent chain that is capable of mechanical action at two distinct stages of the insertion process.

The E3 ubiquitin ligase UHRF1 has been genetically linked to the establishment and maintenance of DNA methylation in mammals. A new study now provides mechanistic insight by demonstrating that binding of UHRF1 to methylated histone H3 lysine 9 during mitosis is needed for stability of DNA methyltransferase 1 and the faithful propagation of DNA methylation.

Both epigenetic and splicing regulation contribute to tumor progression, but how these contributions are linked is not well understood. A new study reveals a cascade of altered gene-expression events that underlie tumor progression, wherein splicing factors Ddx5 and Ddx17 control the alternative splicing of an epigenetic factor, macroH2A1, leading to transcriptional alterations that switch tumor cells to an invasive phenotype.

Type IIA topoisomerases (topos) control supercoiling and disentangle chromosomes by an ATP-dependent strand-passage mechanism. The structure of a full-length budding-yeast topo II in complex with DNA and an ATP analog now provides a picture of its architecture, revealing a structural basis for unidirectional strand passage and a DNA-induced control mechanism for ATP hydrolysis and topo activity.

Previous studies have shown the potential for convergent transcription as a way to induce gene silencing. This Technical Report now demonstrates that introducing convergent transcription plasmids into either fission yeast or mammalian cells can be used to mediate long-term transcriptional gene silencing of endogenous genes, with major advantages over other gene silencing strategies.

Activation of the anaphase-promoting complex/cyclosome (APC/C) depends on disassembly of the mitotic checkpoint complex (MCC), which has been proposed to require CDC20 autoubiquitylation. A new study involving reconstituted recombinant human APC/C supports the view that the APC15 subunit of APC/C localizes near the MCC binding site and mediates CDC20 autoubiquitylation, thereby promoting MCC disassembly.

Procollagen, the precursor of collagen, contains a large C-terminal domain called COLFI that initiates homotrimerization and harbors mutations associated with different diseases. Now the crystal structure of the COLFI domain from human procollagen III is presented, revealing the mechanisms for specificity of trimer formation and the position of disease-related mutations.

Most membrane proteins are co-translationally inserted into the membrane with the aid of Sec-type translocons. Using so-called translation-arrest peptides derived from bacterial and mammalian proteins as natural force sensors, a new study now demonstrates how force is exerted on a nascent chain at two distinct points in a transmembrane helix during its transit through the translocon channel into the membrane.

APOBEC3 (A3) proteins are cytidine deaminases that can restrict retroviral replication by causing hypermutation of the viral genome. The HIV-1 protein Vif counteracts the action of A3s by promoting their degradation. Now the crystal structure of A3C and homology models for A3F and A3DE, together with mutagenesis analyses, allow the identification of their interaction interface with Vif, which is different from a previously implicated region in A3G.

A systematic, unbiased screen for general intronic splicing enhancers (ISEs) identified >100 ISEs that promote intron splicing but inhibit splicing in exons. Putative trans-factors for clusters of ISEs were identified, validated and were found to control ISE activity in a context-dependent manner. Altogether, the data provide a comprehensive picture of how ISEs function depending on their location and cognate trans-factors.

The mechanisms that initiate heterochromatin formation and maintain its distinction from euchromatin have remained elusive. However, a new study reveals a pathway in which transcriptional repression of pericentric repeats by sequence-specific transcription factors is essential for the integrity of heterochromatin, thereby considerably expanding the role of transcription factors beyond euchromatic gene regulation.

The function of nuclear Argonaute proteins in somatic mammalian cells has remained elusive. A new study shows that chromatin-bound Argonaute-1 and Argonaute-2 associate with splicing factors and affect the deposition of histone marks, thereby facilitating spliceosome recruitment and modulating the RNA polymerase II elongation rate. This in turn favors inclusion of variant exons in the mature mRNA.

Rail1 is a component of the mRNA 5′-end quality-control mechanism in yeast. Structural, biochemical and functional studies of its homolog in Kluyveromyces lactis now reveal that the enzyme, dubbed Dxo1, has not only decapping but also 5′-3′ exonuclease activity, enabling it to single-handedly decap and degrade mRNAs from the 5′ end.

The 5-hydroxymethylcytosine (5-hmC) nucleoside is abundant in the brain for unknown reasons. Genome-wide analysis of the distribution of 5-hmC versus 5-methylcytosine (5-mC) in human and mouse tissues now shows that 5-hmC is enriched in genes with synaptic functions. The differential distribution of 5-hmC versus 5-mC at exon-intron boundaries in both human and mouse tissues further suggests a possible role for 5-hmC in pre-mRNA splicing.

The exon junction complex (EJC) links splicing to downstream events including mRNA localization, translation and stability. A combination of in vitro and in vivo approaches were used to identify the splicing factor CWC22 as a direct partner of EJC component eIF4AIII in flies and humans and to demonstrate its functions in preventing eIF4AIII binding to RNA and in escorting eIF4AIII to active spliceosomes before EJC assembly.