Functional characterization of chromatin enriched lncRNAs (cheRNAs) reveals their role as cis-acting transcriptional activators that couple enhancers at sites of cheRNA synthesis to promoters of proximal target genes.
Qingbo Liu, Priyamvada Acharya, Michael A Dolan, Peng Zhang, Christina Guzzo, Jacky Lu, Alice Kwon, Deepali Gururani, Huiyi Miao, Tatsiana Bylund, Gwo-Yu Chuang, Aliaksandr Druz, Tongqing Zhou, William J Rice, Christoph Wigge, Bridget Carragher, Clinton S Potter, Peter D Kwong & Paolo Lusso
Microprocessor components Dgcr8 and Drosha associate with transcriptionally active coding and noncoding genes in a Mettl3-dependent manner and, upon temperature stress, relocate to heat-shock genes, where they mark mRNAs for subsequent degradation.
Jun Lu, Noel Byrne, John Wang, Gerard Bricogne, Frank K Brown, Harry R Chobanian, Steven L Colletti, Jerry Di Salvo, Brande Thomas-Fowlkes, Yan Guo, Dawn L Hall, Jennifer Hadix, Nicholas B Hastings, Jeffrey D Hermes, Thu Ho, Andrew D Howard, Hubert Josien, Maria Kornienko, Kevin J Lumb, Michael W Miller, Sangita B Patel, Barbara Pio, Christopher W Plummer, Bradley S Sherborne, Payal Sheth, Sarah Souza, Srivanya Tummala, Clemens Vonrhein, Maria Webb, Samantha J Allen, Jennifer M Johnston, Adam B Weinglass, Sujata Sharma & Stephen M Soisson
Crystal structures of hGPR40, a target for treatment of type 2 diabetes, bound to a partial and an allosteric agonist explain the binding cooperativity between these ligands and present new opportunities for structure-guided drug design.
MDM2 mutations that prevent E2–ubiquitin binding without altering RING domain structure lead to loss of E3-ligase activity, while the ability to limit p53 transcriptional activity is retained, allowing cells to respond more quickly to cellular stress.
X-ray crystallography and NMR analysis demonstrate that, contrary to previous observations, fC does not significantly alter DNA structure, thus suggesting an alternative basis for recognition of fC-DNA by epigenome-modifying enzymes.
A working model for β-cardiac myosin in the sequestered state and binding assays reveal interactions between the myosin head and tail that are disrupted by mutations associated with hypertrophic cardiomyopathy.
In this Perspective, the authors consider how DNA breaks stimulate R-loop formation, particularly within actively transcribed genomic regions, and discuss the cellular mechanisms that prevent or remove RNA–DNA hybrids to preserve genome integrity.
The human enzyme CTP synthase forms polymeric filaments with increased catalytic activity, in contrast to the inactive filaments formed by bacterial CTP synthase. Cryo-EM and crystallographic analyses explain the structural bases for those different behaviors.
In stressed cells, the ADAR1p110 isoform is phosphorylated and translocated from the nucleus to the cytoplasm, where it protects transcripts with 3′-UTR dsRNA structures from Staufen1-mediated decay, thus suppressing cellular apoptosis.
A novel combination of magnetic tweezers and single-molecule TIRF microscopy reveals that topoisomerase IA makes multiple attempts to engage DNA before successfully catalyzing strand passage and DNA relaxation.
The crystal structure of LptB2FG, an ABC transporter that extracts LPS from the bacterial inner membrane and transports it to the outer membrane, indicates a transport mechanism distinct from classical ABC transporters.
Molecular motor dynein-2, involved in retrograde intraflagellar transport, adopts an autoinhibited conformation, in which the mechanical linker and track-binding stalk are trapped via a newly described motor–motor interface.
Cryo-EM structures of the yeast 40S in complex with ribosome-splitting protein ABCE1, along with functional analyses, reveal that the FeS cluster domain undergoes a 150° rotation to dissociate ribosomal subunits.
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani & Valerio Orlando
Human OGA forms an unusual arm-in-arm homodimer with a substrate-binding cleft that affords extensive interactions with the peptide substrate in a recognition mode distinct from that of its bacterial homologs.
François Aymard, Marion Aguirrebengoa, Emmanuelle Guillou, Biola M Javierre, Beatrix Bugler, Coline Arnould, Vincent Rocher, Jason S Iacovoni, Anna Biernacka, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Peter Fraser & Gaëlle Legube
This Review highlights recent breakthroughs in X-chromosome inactivation and discusses how the multitasking RNA Xist can structurally and functionally transform an active chromosome into uniquely organized facultative heterochromatin.