Research articles

mRNAs have been shown to cross-talk with other mRNAs by serving as competing endogenous RNAs that 'sponge up' microRNAs. A report now claims a new, physiologically significant function for mRNAs that cross-talk through partially complementary Alu elements in the 3′ untranslated region. The Staufen1-mediated mRNA pathway targets both mRNAs in the duplex, provided that they are translated.

4C (chromosome conformation capture on chip) analyses using the clock-controlled Dbp gene as bait reveal the existence of circadian long-range interactions in mouse embryonic fibroblasts. The Dbp circadian interactome is dependent on a functional circadian clock and contains a number of clock-related DNA elements.

p38α MAP kinase is activated by autophosphorylation, which is promoted by the protein TAB1 during myocardial ischemia and other stresses. Now cellular, biochemical and biophysical approaches reveal that TAB1 binds p38α's C-terminal kinase lobe and induces rearrangements within the activation segment that allow autophosphorylation in cis.

Individual microRNAs (miRNAs) can target many mRNAs that form networks of presumably cooperating genes. A new study now tests this idea by screening miRNAs and their targets in the context of dedifferentiation, or reprogramming, of mouse fibroblasts to induced pluripotent stem cells. These data establish two networks of miRNA-mRNA interactions that act together to suppress early stages of reprogramming.

Archaeal glutamate transporter homologs catalyze the coupled uptake of aspartate and sodium ions. A new crystal structure of Glt_Tk from Thermococcus kodakarensis shows the empty transporter oriented in the outward-facing conformation after substrate delivery, revealing how it is reset in preparation for another translocation cycle.

Equivalent mutations in the pseudokinase domain of Jak2 (V617F) and Jak1 (V658F) result in myeloproliferative disorders. Crystal structures of wild-type and the V658F mutant of human Jak1 spanning the pseudokinase domain and a segment of the SH2-PK linker now reveal the existence of a conformational switch that is stabilized by oncogenic mutations and favors activation.

Noncoding telomere repeat–containing RNA (TERRA) expressed from chromosome ends can form RNA-DNA hybrids at telomeres, but how this influences telomere length is unclear. Now, TERRA RNA-DNA hybrids are shown to promote telomere recombination and delay senescence in cells lacking telomerase, establishing a function for TERRA in telomere-length maintenance.

The cancer-associated D2723H mutation causes mislocalization of BRCA2 to the cytoplasm. New work shows that this mutation disrupts the interaction of BRCA2 with DSS1, unmasking a BRCA2 nuclear export signal within the DSS1 binding domain. This impairs nuclear retention of BRCA2 and, consequently, RAD51, suggesting that the intracellular localization of these factors may control their function in maintaining genome integrity.

In the eukaryotic 26S proteasome, a heterohexameric AAA+ complex unfolds substrates prior to degradation. The yeast unfoldase subunits have now been expressed in bacteria and reconstituted into active proteasomes in vitro. Mutations of catalytic and structural motifs in each individual subunits reveal that they play distinct roles in substrate processing, peptidase binding and gate opening.

Although histone H3 Lys4 (H3K4) methylation is widely associated with gene activation, direct evidence for its causal role in transcription is lacking. New studies with the histone methyltransferase MLL2 in a cell-free transcription system now establish a direct causal role for MLL2-mediated H3K4 methylation in transcription and identify AKAP95 as a new modulator of H3K4 methylation.

How the activity of transposable elements is regulated is not well understood. A new study now shows that the Microprocessor complex, which is required for microRNA biogenesis, also recognizes and binds RNAs derived from human LINE-1, Alu and SVA retrotransposons and that it acts as a post-transcriptional repressor of mammalian retrotransposons in vivo.

Ligand-gated ion channels are susceptible to inactivation upon prolonged exposure to their ligand, a process known as desensitization. A sodium-binding pocket within the KAR-type glutamate receptor GluK2 is now shown to have a crucial role in this process, as desensitization is shown to occur only when the ligand is bound without cation pocket occupancy.

The deubiquitinating enzyme OTUB1 binds charged E2 intermediates and prevents ubiquitin transfer. OTUB1 can also bind uncharged E2, and this interaction is now shown to stimulate OTUB1's deubiquitination activity. Thus, OTUB1–E2 complexes might regulate levels of ubiquitin conjugation in response to available free ubiquitin and the ratio of charged to uncharged E2.

Acetylation of the Sir3 N terminus is important for transcriptional silencing in budding yeast and is thought to promote binding of the Sir3 BAH domain to the nucleosome. Structural and biochemical analyses now demonstrate that the acetylated Sir3 N terminus does not interact with the nucleosome directly but instead stabilizes a nucleosome-binding loop in the BAH domain.

N-terminal acetylation of Sir3 is essential for heterochromatin establishment and maintenance in yeast, but its mechanism of action is unknown. The crystal structure of the N-terminally acetylated BAH domain of Sir3 bound to the nucleosome core particle revealed that N-terminal acetylation stabilizes the interaction of Sir3 with the nucleosome.

Embryonic stem cells (ESCs) possess a unique chromatin landscape in which 'bivalent' domains of trimethylated histone H3 Lys4 (H3K4me3) and Lys27 (H3K27me3) mark key lineage-specific genes. A new study now reports the identification of Mll2 (KMT2b) as the enzyme responsible for implementing H3K4me3 on bivalently marked promoters in ESCs.

Measuring gene expression in individual cells is crucial for understanding the gene regulatory network controlling human embryonic development. Single-cell RNA sequencing (RNA-Seq) analysis of 124 individual cells from human preimplantation embryos and embryonic stem cells (hESCs) now provides a comprehensive framework of the transcriptome landscapes of human early embryos and hESCs.

The crystal structure of the full catalytic core of p300 reveals the presence an unexpected RING domain, within the CH2 region, that folds over the HAT-domain substrate-binding pocket. Mutations that destabilize the RING-HAT interaction and increase acetyltransferase activity in vitro are also found in B-cell lymphomas, thus suggesting an important function for this autoinhibitory interaction in vivo.

How plant pri-miRNAs with complex secondary structures are recognized and processed has been unclear. A new study now suggests that unlike canonical processing of pri-miRNAs, terminal loop–branched pri-miRNAs can be processed by Dicer-like 1 (DCL1) complexes bidirectionally, either from the lower stem to the terminal loop or vice versa, resulting in productive and abortive processing of miRNAs, respectively.

Proteins containing repeats of the WASP homology 2 (WH2) actin-binding module are multifunctional regulators of actin nucleation and assembly. Now biochemical analyses of VopF from Vibrio cholerae reveal a new regulatory mechanism of actin-filament barbed-end dynamics including enhanced nucleation, uncapping and assisted elongation.