Volume 25 Issue 4, April 2018

Recent developments in transcriptome-wide sequencing technologies have enabled the identification of cellular mRNA decay intermediates. Although canonical mRNA decay has been shown to occur by deadenylation followed by decapping and subsequent exonucleolytic decay from both mRNA ends, a study by Mourelatos and colleagues now defines mRNA fragments that are generated on polysomes by endonucleolytic cleavages phased by the associated ribosome.

Using Akron-seq, a novel approach that captures native 3′ and 5′ ends of capped and polyadenylated RNAs, Mourelatos and colleagues show that mRNAs are subject to repeated cotranslational endonucleolytic cuts at the ribosome exit channel.

Structural analyses of fibrils formed by segments from human TDP-43 RRM2 reveal extensive packing and positional polymorphism.

Interaction-energy analyses of the interfaces between voltage-sensor and pore domains of the Shaker K⁺ channel reveal the role of contacts between S4 and S5 in electromechanical coupling in addition to the canonical pathway through the S4–S5 linker.

A lag in nascent strand DNA methylation contributes to heterogeneous methylation in asynchronous cell populations, but cancer cells and active transcription factor binding sites preserve heterogeneity even after cell cycle arrest.

Cryo-EM structures of human ABCG2 bound to synthetic derivatives of inhibitor Ko143 or the multidrug resistance modulator tariquidar together with insight into the structure–activity relationship of the Ko143 scaffold provide a basis for the design of novel ABCG2 inhibitors.

Two segments from FUS LC are shown to form reversible fibrils. The structural bases for this behavior and for its regulation by phosphorylation is revealed using X-ray and microelectron diffraction.

Single-molecule FRET analysis of DNA binding and unwinding by two engineered Cas9s reveals that their improved specificity is achieved through lower binding and more transient unwinding of mismatched DNA and lower intrinsic cleavage reaction rates.