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A new high-throughput sequencing method to determine mRNA poly(A)-tail length enabled studies of individual RNAs across species and developmental stages to investigate the role of poly(A) length in translational regulation; the relationship between poly(A) length and translational efficiency shown in early embryo systems does not occur later in development, a finding that explains different regulatory consequences of microRNAs acting at different developmental times.
This study defines how a short DNA sequence, known as the PAM, is critical for target DNA interrogation by the CRISPR-associated enzyme Cas9 — DNA melting and heteroduplex formation initiate near the PAM and extend directionally through the remaining target sequence, and the PAM is also required to activate the catalytic activity of Cas9.
One of two papers describing a reprogramming phenomenon called stimulus-triggered acquisition of pluripotency (STAP) — in STAP, lineage-committed adult somatic cells are reprogrammed to pluripotency by transient exposure to low-pH treatment, and extensive analysis of the molecular features and developmental potential of STAP cells indicates that they represent a unique state of pluripotency.
A short hairpin RNA screen to identify genes that modify the action of tumour-infiltrating CD8 T cells in tumour-bearing mice pinpointed the phosphatase subunit Ppp2r2d as a new target for tumour therapy; knockdown of Ppp2r2d in T cells enabled their accumulation in tumours and significantly delayed tumour growth.
Single-cell- and metagenomics-based study reveals two members of the candidate genus ‘Entotheonella’, symbionts of the marine sponge Theonella swinhoei; distinct biosynthetic gene clusters that account for most of the bioactive polyketides and peptides known from T. swinhoei are shown to be attributable to a single member of the T. swinhoei Y microbiome.
This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.
Through the use of a novel three-dimensional imaging technique, used in conjunction with a multicolour reporter that allows lineage tracing and cell tracking of entire mammary ducts in vivo, bipotent stem cells are shown to have a central role in both puberty and long-term maintenance; in addition, long-lived luminal progenitor cells with a prominent role in ductal expansion are identified.
The authors report the largest family-trio exome sequencing study of schizophrenia to date; mutations are overrepresented in genes for glutamatergic synaptic proteins and also genes mutated in autism and intellectual disability, providing insights into aetiological mechanisms and pathopshyisology shared with other neurodevelopmental disorders.
Exome sequence analysis of more than 5,000 schizophrenia cases and controls identifies a polygenic burden primarily arising from rare, disruptive mutations distributed across many genes, among which are those encoding voltage-gated calcium ion channels and the signalling complex formed by the ARC protein of the postsynaptic density; as in autism, mutations were also found in homologues of known targets of the fragile X mental retardation protein.
Evolutionary study of long noncoding RNA (lncRNA) repertoires and expression patterns in 11 tetrapod species identifies approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have ancient origins; many lncRNAs, particularly ancient ones, are actively regulated and may function mainly in embryonic development.
The 1.8 Å high-resolution X-ray crystal structure of the human δ-opioid receptor is presented, with site-directed mutagenesis and functional studies revealing a crucial role for a sodium ion in mediating allosteric control in this receptor.
UvrD acts in nucleotide excision repair by using its helicase/translocase activity to induce RNA polymerase backtracking, enabling repair enzymes to access DNA lesions.
Whole-genome analysis of the elephant shark, a cartilaginous fish, shows that it is the slowest evolving of all known vertebrates, lacks critical bone formation genes and has an unusual adaptive immune system.
Large-scale genomic analysis of somatic point mutations in exomes from tumour–normal pairs across 21 cancer types identifies most known cancer genes in these tumour types as well as 33 genes not known to be significantly mutated, and down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies.
The change in global mean temperature in response to a change in external forcing is highly uncertain; here differences in the simulated strength of convective mixing between the lower and middle tropical troposphere are shown to explain about half of the variance in climate sensitivity, constraining the predicted equilibrium climate sensitivity to an increase of 3 to 5 degrees Celsius.