Volume 22 Issue 4, April 2015

Circadian regulation of epigenetic chromatin marks drives daily transcriptional oscillation of thousands of genes and is intimately linked to cellular metabolism and bioenergetics. New work links circadian fluctuations in the activity of the SIRT1 deacetylase, a sensor of the cellular energy state, to histone-methylation changes and the circadian expression of clock-controlled genes.

Pioneering studies in voltage-gated potassium channels have described movement of the voltage-sensing domain (VSD) S4 helix across the membrane electric field in molecular detail, but much less is known regarding opening of the intrinsic proton pore within VSDs of voltage-dependent proton channels. By systematically probing local kinematics, a new study reveals that movements in helix S1 correlate with pore opening and are distinct from voltage-sensing movements of the charged S4 segment.

Transcriptional termination is an important yet incompletely understood aspect of gene expression. Proudfoot, Jopling and colleagues now identify a new Microprocessor-mediated mechanism of transcriptional termination, which acts specifically on long noncoding transcripts that serve as microRNA precursors.

Voltage- and patch-clamp fluorometry reveal structural rearrangements of the S1 helix and its surroundings that are important for gating of the Hv1 voltage-gated proton channel.

In the absence of RNase H2, ribonucleotides incorporated during DNA replication can be processed by Top1. This activity is directed to the nascent leading strand, because gaps in the lagging strand would limit torsional tension.

Though related to high-fidelity replicases, DNA Pol ν performs mutagenic DNA synthesis. These properties are now explained by structural and biochemistry analyses of human DNA Pol ν revealing conformational changes involving the finger and thumb domains.

DNA polymerase θ is involved in alternative end-joining repair of DNA double-strand breaks. Structural and biochemical analyses shed light on pol θ's ability to prime DNA synthesis from nonoptimal base-pairing.

MLL1 regulates circadian promoters by depositing H3K4 trimethyl marks, whose levels are also modulated by the NAD⁺-dependent deacetylase SIRT1. SIRT1 is now shown to promote circadian deacetylation of MLL1, thus affecting MLL1's methyltransferase activity.

The finding that miRNA transcripts originating from long-noncoding-RNA loci use Microprocessor, rather than canonical cleavage and polyadenylation, to terminate transcription establishes a new RNase III–mediated transcriptional-termination pathway.

New biochemical and genetic analyses in S. pombe show that Argonaute must be loaded with small RNAs to promote association of the GW-protein components required to assemble a functional transcriptional silencing complex.

High-resolution structure of the E. coli ribosome highlights rRNA and protein modifications and provides details on solvation characteristics and the structural impacts of ribosome modifications.

High-resolution crystal structures of Thermus thermophilus ribosomes reveal previously unseen modifications of rRNA and their contacts with mRNA and tRNAs or the protein pY.

EM analyses reveal the architecture of cytoplasmic dynein in complex with dynactin and the BicD2 cargo adaptor on microtubules, showing the quaternary complex positioned for unidirectional movement and cargo recruitment.