Transcriptome-wide splicing network reveals specialized regulatory functions of the core spliceosome.

The spliceosome is the complex molecular machinery that sequentially assembles on eukaryotic messenger RNA precursors to remove introns (pre-mRNA splicing), a physiologically regulated process altered in numerous pathologies. We report transcriptome-wide analyses upon systematic knock down of 305 spliceosome components and regulators in human cancer cells and the reconstruction of functional splicing factor networks that govern different classes of alternative splicing decisions. The results disentangle intricate circuits of splicing factor cross-regulation, reveal that the precise architecture of late-assembling U4/U6.

mutation-mediated sensitization to H3B-8800 splicing inhibitor in chronic lymphocytic leukemia.

Splicing factor 3B subunit 1 (SF3B1) is involved in pre-mRNA branch site recognition and is the target of antitumor-splicing inhibitors. Mutations in are observed in 15% of patients with chronic lymphocytic leukemia (CLL) and are associated with poor prognosis, but their pathogenic mechanisms remain poorly understood. Using deep RNA-sequencing data from 298 CLL tumor samples and isogenic WT and K700E-mutated CLL cell lines, we characterize targets and pre-mRNA sequence features associated with the selection of cryptic 3' splice sites upon mutation, including an event in the gene relevant for activation of NF-κB signaling.

Insplico: effective computational tool for studying splicing order of adjacent introns genome-wide with short and long RNA-seq reads.

Although splicing occurs largely co-transcriptionally, the order by which introns are removed does not necessarily follow the order in which they are transcribed. Whereas several genomic features are known to influence whether or not an intron is spliced before its downstream neighbor, multiple questions related to adjacent introns' splicing order (AISO) remain unanswered. Here, we present Insplico, the first standalone software for quantifying AISO that works with both short and long read sequencing technologies.

IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation.

The persistence of latent HIV reservoirs allows for viral rebound upon antiretroviral therapy interruption, hindering effective HIV-1 cure. Emerging evidence suggests that modulation of innate immune stimulation could impact viral latency and contribute to the clearing of HIV reservoir. Here, the latency reactivation capacity of a subclass of selective JAK2 inhibitors was characterized as a potential novel therapeutic strategy for HIV-1 cure.

Computational Analysis of Alternative Splicing Using VAST-TOOLS and the VastDB Framework.

Alternative splicing (AS) can vastly expand animal transcriptomes and proteomes. Two main open questions in the field are how AS is regulated across cell/tissue types and disease, and what roles different AS events play. To facilitate AS research, we have created the computational VastDB framework, which comprises a series of complementary software and resources that we describe in this chapter.