Articles in 2012

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.

In this issue of NSMB, we have opened our pages to the research community to express their thoughts about the importance of the Biological Magnetic Resonance Bank as it copes with budget cuts and faces the termination of its funding from the National Library of Medicine in 2014.

A number of events must occur to preserve the integrity of the chromatin template during gene transcription. A study in this issue reveals a novel mechanism whereby chromatin remodelers are recruited to histone modifications within gene bodies to prevent aberrant histone exchange during transcriptional elongation.

Eukaryotic ribosomal subunits are assembled in the nucleus and exported in a functionally inactive state to the cytoplasm, where they undergo final maturation steps before initiating translation. In the case of pre-40S subunits, these steps involve cleavage of the 20S pre-rRNA to the mature 18S rRNA. Two recent studies have surprisingly revealed that mature 60S subunits, aided by the translation initiation factor eIF5b (known as Fun12 in yeast), bind pre-40S subunits to assess their translation 'potential' before triggering cleavage of 20S pre-rRNA.

One of the surprising discoveries in the genomic age was the presence in plant genomes of two noncanonical DNA-dependent RNA polymerases involved in small RNA–mediated gene silencing. Two recent studies map the binding sites of RNA polymerase V, uncovering new mysteries concerning the targeting and function of this enigmatic enzyme.

The Biological Magnetic Resonance Bank (BMRB) is facing the threat of having its funding discontinued. Concerned about this situation, the editors of Nature Structural & Molecular Biology have asked the community why it is important to continue to support the BMRB. We have also asked John Markley, head of the BMRB, to present his case.

NMR relaxation phenomena give insight into local protein motions, and understanding protein dynamics can aid in understanding protein function. Nuclear Overhauser enhancements (NOEs) have been traditionally used to determine protein structure by NMR, but a novel application using exact NOEs provides a structural ensemble that describes a protein's structure as well as its dynamics.

Synaptotagmin promotes SNARE-mediated membrane fusion in a Ca²⁺-dependent manner, but the mechanism by which it acts is still unclear. In vitro studies have shown that synaptotagmin can make interactions with its own vesicle membrane, inhibiting its ability to stimulate fusion with target membranes. New data now suggest that ATP and other polybasic anions may have a role in directing synaptotagmin to its target membrane in vivo.