Volume 19 Issue 9, September 2012

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.

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.

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.

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.

Plant RNA Pol V is involved in the RNA-directed DNA-methylation pathway that leads to heterochromatic silencing at some endogenous loci. Now the genomic regions targeted by Pol V in Arabidopsis thaliana are determined by ChIP-seq analyses revealing Pol V's enrichment at evolutionarily recent transposons.

RING domain–containing E3 ligases promote the transfer of ubiquitin from the active site of an E2 to acceptor lysine residues on substrates, but the mechanism by which this occurs was unclear. Structural and biochemical studies using the E3 BIRC7 and E2 UbcH5b indicate that the E3 properly orients and stabilizes the ubiquitin-charged E2 to promote an efficient transfer reaction.

The histone H3K36 methylation mark is associated with coding regions of actively transcribed genes, yet it plays a negative role during transcription elongation. In vitro and in vivo studies in budding yeast now reveal that the Isw1b chromatin remodeler is recruited by H3K36 methylation to open reading frames, where it acts in conjunction with a second remodeler to prevent histone exchange and maintain chromatin integrity during transcription elongation.

HIV-1 virions interact with host-cell receptors via the trimeric envelope glycoprotein (Env) consisting of gp120 and gp41 polypeptides. Single-particle cryo-EM is now used to reconstruct the structure of membrane-bound Env trimer in its unliganded state, revealing a cage-like architecture and allowing the identification of interprotomer contacts.

Although cytosine-C5 methylation is a prominent modification of tRNAs, its functional significance has been unclear. Mice that lack both the Dnmt2 and NSun2 tRNA methyltransferases showed developmental and cellular differentiation defects, and loss of Dnmt2 and NSun2 was further associated with tRNA degradation and reduced rates of protein synthesis, suggesting that this modification promotes mouse development by supporting protein synthesis.

Nectins and nectin-like proteins promote intercellular adhesion and tissue patterning in vertebrates through homophilic or heterophilic interactions. Now the formation of all the possible nectin pairs is studied systematically in vitro, and crystal structures provide insight into the molecular basis for the adhesive binding specificity of nectins.

Tumor suppressor protein p53 interacts with and is acetylated by PHF20, but the consequences of this association were not clear. Now PHF20 is shown to be a direct regulator of p53, with its Tudor domain recognizing p53 modified with dimethyl groups at Lys370 or Lys382. This association promotes p53's stabilization and activation during the DNA-damage response, by inhibiting the association of Mdm2 with p53.

Kinetochores are large structures composed of hundreds of proteins that assemble onto centromeric DNA to form a microtubule-binding site that is essential for proper chromosomal segregation. The structure of budding-yeast kinetochore particles is now studied by EM and electron tomography, revealing a large central hub surrounded by multiple globular domains, and multiple attachment sites for microtubules.

Histone gene transcription is downregulated after DNA synthesis is completed, but how cells terminate histone gene transcription has been unknown. A new study uncovers that phosphorylation of histone H2B at Tyr37 by WEE1 kinase leads to a coordinated transcriptional repression of replication-dependent core histone genes in the late S/G2 phase in yeast and mammalian cells.

The human colony-stimulating factor (hCSF-1) cytokine is essential for innate and adaptive immune responses. The Epstein-Barr virus protein BARF1 binds to hCSF-1, preventing interferon-α secretion. Structural and functional data reveal a new mechanism for the antagonism of human but not mouse CSF-1 signaling by BARF1.

Telomeres have the ability to repress expression of nearby genes, a phenomenon known as telomere position effect (TPE). Telomeric RNA species called TERRA now allow assessment of whether TPE exists at human chromosome ends. Telomere elongation is found to repress TERRA expression, which is mediated by increased trimethylation of telomeric H3K9 and by heterochromatic protein HP1α.

Antibiotics target protein synthesis by binding and inhibiting key functional centers of the ribosome. Single-molecule imaging and X-ray crystallography studies now demonstrate that the aminoglycoside antibiotic neomycin binds to ribosomal RNA within the large subunit to allosterically control ribosomal subunit rotation and stabilize an inactive configuration of the ribosome.

The structure-specific endonucleases Mus81-Mms4 and Yen1 are involved in the resolution of Holliday junctions and in crossover formation in the budding yeast. Now genetic work implicates the nucleotide excision repair nuclease complex Rad1-Rad10 in the processing of recombination intermediates formed between substrates with limited homology.