Volume 21 Issue 7, July 2014

ATP is continuously synthesized inside mitochondria and exported to the cytoplasm via transporter and channel proteins residing in the inner and outer mitochondrial membranes, respectively. In this issue of Nature Structural & Molecular Biology, a new crystal structure of the mitochondrial channel protein VDAC-1 provides the basis for a detailed simulation study that unravels the mechanism by which ATP diffuses across the outer mitochondrial membrane at a fast rate.

Post-transcriptional mRNA regulation is often attained by lengthening or shortening the 3′ poly(A) tail of a transcript. Eukaryotic mRNAs show a spectrum of deadenylation rates, thus allowing intricate control of gene expression, but the mechanisms that determine such rates are unclear. Three new studies highlight the structural and biochemical features of a key enzyme in removing poly(A) tails, the PAN2–PAN3 complex, providing clues to how different mRNA deadenylation rates can be achieved.

Cancer-associated mutations in the pseudokinase domain (JH2) of JAK2 lead to constitutive activation of its tandem kinase domain (JH1). Molecular dynamics simulations, supported by mutational analysis, provide a model for JH2-JH1 interactions that explains many of the JAK2-activating disease mutations.

Chang and colleagues report the involvement of a Dicer-microRNA-cMyc signaling axis in the transcriptional regulation of a large set of long noncoding RNAs (lncRNAs). These lncRNAs are specifically dependent on cMyc, as compared to divergently transcribed protein-coding genes.

Conti and colleagues present the crystal structure of the yeast deadenylase Pan2–Pan3 core complex, revealing a 1:2 stoichiometry and indicating how deadenylase and pseudokinase domains work together to promote RNA deadenylation.

Structural analyses reveal the asymmetric assembly of Neurospora crassa PAN2–PAN3 complex and, along with functional work on the proteins from different species, indicate an essential role for PAN3 in coordinating PAN2-mediated deadenylation with subsequent steps in mRNA decay.

A new study using fertilized mouse eggs shows that nuclear pore complex (NPC) formation is dependent on nucleosome assembly. Preventing de novo histone deposition on sperm chromatin results in formation of a paternal nuclear envelope lacking NPCs, thus indicating a role for nucleosomes beyond DNA packaging.

A new system to monitor the effects of nucleosome depletion in Xenopus egg extracts reveals that nucleosomes are required for spindle assembly and for recruitment of nuclear pore complex (NPC) components to the nuclear envelope for NPC formation.

VDAC channels permeate metabolites from the mitochondrial intermembrane space to the cytosol. Markov state modeling, an approach used in protein-folding simulations, is now applied to examine ATP-permeation rates and pathways through mouse VDAC1.

The X-ray crystal structure and biochemical analysis of a triple helix formed between the expression and nuclear retention element (ENE) and the 3′ poly(A) tail of the human long noncoding RNA MALAT-1 reveals the basis of its stability and how it confers resistance to degradation.

The first comprehensive analysis of the meiotic translational program of Schizosaccharomyces pombe by deep sequencing of ribosome-protected fragments identifies new translated sequences and highlights differences in the translational changes occurring during sexual differentiation of fission and budding yeasts.