Search

Most human genes undergo alternative splicing, but population-level variation is poorly understood. Here, the authors map over 57,000 naturally variable exons across 838 individuals, revealing widespread splicing diversity and its impact on gene expression and genetic interpretation.

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 biophysical model uses knockdown or overexpression data to infer splicing factor activity.

Non-coding introns are excised from RNA transcripts of most eukaryotic genes by splicing. Here, Kenny et al. show that LUC7 proteins promote the splicing of different subsets of introns with distinct 5′ splice site sequences, and that these preferences are conserved from plants to human.

This study details how RNA-binding sites evolved between human and mouse, focusing on the conserved neuronal protein, Unkempt. The authors uncover that RNAbinding proteins often change binding sites and regulation across species even when binding motifs are conserved.

Moderate-affinity ‘secondary’ Rbfox binding motifs regulate RNA splicing during neuronal development in a manner that is dependent on Rbfox concentration.

Identifying functional genetic variants in non-coding regions of the human genome is challenging. Here the authors apply their iMAPS approach to 3ʹ untranslated regions, identifying thousands of variants that disrupt post-transcriptional gene regulation.

Scrutinizing the empirical evidence for bidirectional trade-offs in fine root traits, the authors show that while these are important in explaining species occurrences along broad temperature and water availability gradients, unidirectional benefits are prevalent.

Venous tumour thrombus can occur within renal cell carcinoma, and can require complex additional surgery and treatment. Here, the authors analyse multiparametric data from patients treated with axitinib and develop a machine learning model to predict neoadjuvant treatment response.

Joint analysis of new and previously published sequencing data for primary and metastatic prostate cancers identifies new candidate driver mutations and provides insights into disease progression and potential drug targets.

Differential binding of RNA-binding proteins mediated by genetic variants (GVs) can influence posttranscriptional regulation. Here, the authors develop BEAPR, a computational approach to identify allele-specific binding events in eCLIP-Seq data.

Alternative splicing increases genome coding potential and is affected by factors including the hnRNPs. The effect of altering splice site strength on splicing activity is now found to be antagonized by nearby hnRNP H binding sites. Other splicing factor sites may have similar effects and may thus have influenced splice form evolution.

This paper reports on an intensive bioinformatic analysis of human alternative splicing in various tissues and cancers. The analysis offers insight into tissue specificity, coordinated regulation and sequence conservation of alternative splicing. Evidence is also obtained that alternative splicing is mechanistically linked to a modification of mRNAs known as polyadenylation.

The mixture of isoforms model (MISO) assesses the confidence in estimates of the abundance of spliced exons or isoforms from paired-end RNA-seq data and detects their differential expression.

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

Abnormal functions of RNA-binding proteins TAF15, FUS and TDP43 are associated with amyotrophic lateral sclerosis. Here, Kapeli et al. characterize the RNA targets of TAF15 and identify points of convergence and divergence between the targets of TAF15, FUS and TDP43 in several neuronal systems.

Alternative splicing is a process during gene expression that increases the diversity of proteins encoded by a single gene. Here, the authors perform RNA-sequencing on cardiac cells from mice and show that extensive changes in gene expression and alternative splicing occur during the first month after birth.

A cell-based screen for intronic splicing silencers revealed ten sequence motifs that inhibited splicing in human cells and either enhanced or inhibited exon inclusion when inserted into exons. Identification of trans-acting splicing factors for each motif revealed a complex network, which suggests that cis elements function differently in distinct cellular contexts, depending on the regulatory factors present.

The role of the genome structure in the establishment of the embryonic and trophoblast lineages is still not well understood. Here the authors perform promoter capture Hi-C in mouse trophoblast and embryonic stem cells and find divergent networks of repressive and active chromatin interactions between the two lineages.

Although a first draft of the human genome is now available, our knowledge of the set of transcripts expressed from this sequence is still far from complete. A new method using ink-jet microarray technology to experimentally test predicted exons provides a genome-based platform for gene identification that bypasses an important limitation of older technologies based on cDNA libraries.

Nutiu et al. repurpose an Illumina sequencer to quantitatively measure binding affinities between protein and DNA. The data reveal the complex interdependency among binding motif positions and allow improved prediction of gene expression.

This study identifies MBNL proteins as negative regulators of alternative splicing events that are differentially regulated between ES cells and other cell types; several lines of evidence show that these proteins repress an ES cell alternative splicing program and the reprogramming of somatic cells to induced pluripotent stem cells.

Asymmetric sequence determinants flanking gene transcription start sites are shown to control directionality of transcription elongation in mammalian cells by regulating promoter-proximal cleavage and polyadenylation.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

Using genomic data, this Analysis demonstrates that commonly inherited single nucleotide polymorphisms (SNPs) occurring in genes of the p53 pathway affect the incidence of a broad range of cancers, more so than SNPs in other pathways. This has implications for p53-mediated tumour suppression in humans.

In diploid organisms, expression from only one allele is frequently observed. This Review focuses on the widespread random monoallelic expression (RME) of autosomal genes, highlighting both the mitotically stable form observed in bulk analyses of cell populations and the recently discovered dynamic form identified through single-cell studies. The article also addresses the implications of different experimental criteria for calling monoallelic expression and potential biological roles in disease manifestations.