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Sequencing the genome and microbiome of about 1,500 tick samples from regions across China revealed host–microbe associations in ticks that could have implications for controlling ticks and tick-borne diseases.

Cheng et al. identify a mitochondrial complex IV (CIV) deficiency in the brains of patients with sporadic amyotrophic lateral sclerosis (ALS). They demonstrate that defects in mitochondrial CIV induce ALS-like phenotypes in rats and highlight CIV deficiency as a potential risk factor and therapeutic target for ALS.

This protocol describes the steps in R-ChIP, a procedure based on chromatin immunoprecipitation (ChIP) of an exogenously expressed mutant RNASEH1 to capture the genome-wide distribution of R-loops.

CSB deficiency is associated with induction of R-loops and genome instability, impacting long genes linked to neuronal functions in humans. Here the authors provide mechanistic understanding on how mutations in the CSB gene affects RNAPII elongation and genome instability.

A combination of five assays is used to produce a catalogue of RNA elements to which RNA-binding proteins bind in human cells.

U2AF is known to affect 3′-splice-site selection. Here, Fu and colleagues use genome-wide analysis of U2AF-RNA interactions to define U2AF's key roles in gene expression and regulated splicing in normal and disease states.

A neutron star candidate in a close binary has been discovered using a radial velocity method and characterized with a variety of ground- and space-based telescopes. The system probably represents an underexplored population of non-accreting and/or non-beaming neutron stars.

Genome-wide profiles of RNA–chromatin interactions in Arabidopsis reveal the types of RNAs that mediate cis, intra-chromosomal and inter-chromosomal interactions and suggest the formation of co-regulatory gene expression networks in response to stresses.

Depletion of the RNA-binding protein PTB (also known as PTBP1) in astrocytes reprograms these cells to become functional neurons and, in a mouse model of Parkinson’s disease, reverses the disease phenotype.

The role of glycolysis in depression is unclear. Here the authors report a glycolytic deficit under social stress and demonstrate that astrocytic LDHA affects neuronal excitability and depressive-like behaviours via lactate homeostasis in mice.

Dominant mutations in the RNA-binding protein FUS/TLS cause amyotrophic lateral sclerosis (ALS), an adult-onset motor neuron degenerative disease. Here, the authors show that ALS-causative FUS/TLS mutations directly bind the SMN and U1-snRNP complexes, producing both loss and gain of function effects on RNA processing.

Karni et al. report in this issue that proteins in the SR family, which modify gene function by alternative splicing, are among the many factors that can transform mammalian cells to malignancy. These splicing proteins regulate alternative splicing of many known proto-oncogenes and tumor-suppressor genes, thereby activating them post-transcriptionally to allow cells to escape normal controls on cell growth and proliferation.

Hippo signalling is reported to be required for proper ESR1 expression. Here the authors reveal that the transcriptional repression of ESR1 is via LATS-YAP-TEAD-VGLL3 axis and the epigenetic regulation of ESR1 super enhancer in ER + breast cancer.

Wiskott-Aldrich syndrome is caused by mutations in WASP, but the underlying mechanisms remain to be explored. Here the authors reveal that WASP deficiency results in aberrant RNA splicing, and that WASP regulates the transcription of splicing factor genes and co-transcriptional RNA splicing via a phase-separation process that involves splicing factors and nascent RNA.

New data reveal a sequential mode of alternative polyadenylation. Distal polyA sites are processed first and the resultant transcripts are retained in the nuclear-chromatin matrix for subsequent cleavage and polyadenylation at proximal polyA sites.

Cytoplasmic aggregates of TDP-43 sequester specific miRNAs and subsets of proteins, causing dysregulation of mitochondrial proteins and a global mitochondrial imbalance that augments oxidative stress and may promote ALS initiation and progression.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

A new class of miRNA-recognition elements that function exclusively in protein-coding regions use distinct target-recognition rules and mediate translational repression instead of mRNA destabilization.

Using CLIP-seq technology, the genome-wide binding sites of the FOX2 splicing regulator in human embryonic stem cells (hESCs) are now identified. Further work based on FOX2 depletion uncovers the underlying logic of FOX2-mediated regulation of alternative splicing and finds that such compromised hESCs undergo rapid cell death.

It is known that components of the splicing machinery are guided to nascent transcripts through interactions with the Pol II transcriptional complex. Data now indicate that depletion of SC35, a splicing factor, leads to defective elongation as well as reduced Pol II phosphorylation and association with elongation factors. This leads to a model where components of the splicing machinery have a role in promoting elongation of the transcriptional machinery.

The RNAs bound to the genome and their binding sites are detected with GRID-seq.

Labeling newly transcribed RNA with 5-ethynyluridine and adding biotin via click chemistry allows the analysis of the proteome bound to the various RNA species, including nascent RNA.

The lncRNA NEAT1, a key component of paraspeckles, interacts with RNA-binding proteins, including NONO and PSF, and affects global pri-miRNA processing by recruiting the Drosha–DGCR8 Microprocessor.

The authors reveal that PTB and its homolog nPTB mediate two sequential RNA regulatory loops required for converting human adult fibroblasts to functional neurons, and likely required for neurogenesis in vivo. The first loop, PTB–miR-124–REST, controls initial neuronal conversion and the second, nPTB–miR-9–BRN2, is responsible for neuronal maturation.

The metavirome of 31 tick species sheds light on the diversity and distinct evolution of tick-associated RNA viruses, and lays the foundation for better understanding of tick–virus interaction.

p63 and PAX6 act to specify limbal stem or progenitor cells (LSCs), and WNT7A controls corneal epithelium differentiation through PAX6; loss of WNT7A or PAX6 induces LSCs into epithelium, and transduction of PAX6 in skin epithelial stem cells converts them to LSC-like cells and transplantation in a rabbit corneal injury model can replenish corneal epithelial cells and repair damaged corneal surface.

RNA-binding proteins (RBPs) influence alternative splicing in a highly context-sensitive and combinatorial manner, and it is therefore difficult to predict their actions on the basis of genomic sequence. However, recent progress in understanding alternative splicing, particularly using global approaches, has revealed new sets of rules for deciphering these patterns. This Review outlines the function of RBPs at different levels and describes the emerging rules of alternative splicing.

Enabled by genome-wide profiling approaches, there is growing appreciation for the prevalence and functional importance of various types of chromatin-associated RNAs. As Li and Fu describe in this Review, these RNAs can either be retained in cis at their site of transcription or recruited in cis to other loci, and they have diverse roles in gene regulation, genome organization, nuclear body formation and phase-separation events.

Circadian rhythms regulate a wide variety of developmental and metabolic processes resulting in enhanced fitness. In this study, a link is made between plant immune responses and the circadian clock. Plant defence against a fungal pathogen which causes downy mildew disease in Arabidopsis is studied, and it is shown that a novel set of defence genes are regulated by the circadian regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1). The mechanism allows plants to 'anticipate' infection at dawn when the pathogen normally disperses its spores. Such a cross-talk mechanism reveals an important strategy for plants to time immune responses against pathogens.

Structural and biochemical studies of RNA polymerase II (Pol II) assembled on DNA containing 5-carboxycytosine reveals that Pol II can sense the oxidized methylation state of DNA and transiently slows down during transcription.

A non-coding region on chromosome 9p21 was previously shown to associate with coronary artery disease and type 2 diabetes, and the region has been implicated in regulating neighbouring genes. Here, 33 distinct enhancers within this region are identified, showing that SNPs in one of the enhancers affect STAT1 binding. Furthermore, it is shown that in human vascular endothelial cells the enhancer interval physically interacts with a number of specific loci and that IFN-γ activation strongly affects the chromatin structure and transcriptional regulation of the 9p21 locus, including STAT1 binding, long-range enhancer interactions and expression of neighbouring genes.