DNMT3B splicing dysregulation mediated by SMCHD1 loss contributes to DUX4 overexpression and FSHD pathogenesis.

Structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) is a noncanonical SMC protein and an epigenetic regulator. Mutations in SMCHD1 cause facioscapulohumeral muscular dystrophy (FSHD), by overexpressing DUX4 in muscle cells. Here, we demonstrate that SMCHD1 is a key regulator of alternative splicing in various cell types.

Niche partitioning and individual specialisation in resources and space use of sympatric fur seals at their range margin.

Ecological theory predicts niche partitioning between high-level predators living in sympatry as a mechanism to minimise the selective pressure of competition. Accordingly, male Australian fur seals Arctocephalus pusillus doriferus and New Zealand fur seals A. forsteri that live in sympatry should exhibit partitioning in their broad niches (in habitat and trophic dimensions) in order to coexist.

The spectrum of pre-mRNA splicing in autism.

Disruptions in spatiotemporal gene expression can result in atypical brain function. Specifically, autism spectrum disorder (ASD) is characterized by abnormalities in pre-mRNA splicing. Abnormal splicing patterns have been identified in the brains of individuals with ASD, and mutations in splicing factors have been found to contribute to neurodevelopmental delays associated with ASD.

Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome.

Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WW domain-binding protein 4 (WBP4) is part of the early spliceosomal complex and has not been previously associated with human pathologies in the Online Mendelian Inheritance in Man (OMIM) database. Through GeneMatcher, we identified ten individuals from eight families with a severe neurodevelopmental syndrome featuring variable manifestations.

Isoforms of the TAL1 transcription factor have different roles in hematopoiesis and cell growth.

T-cell acute lymphoblastic leukemia (T-ALL) protein 1 (TAL1) is a central transcription factor in hematopoiesis. The timing and level of TAL1 expression orchestrate the differentiation to specialized blood cells and its overexpression is a common cause of T-ALL. Here, we studied the 2 protein isoforms of TAL1, short and long, which are generated by the use of alternative promoters as well as by alternative splicing.

Native RNA Immunoprecipitation (RIP) for Precise Detection and Quantification of Protein-Interacting RNA.

Proteins with either RNA or DNA-binding motifs were shown to bind RNA. Immunoprecipitation of such proteins using antibodies and identification of the RNA-binding molecules is called RNA immunoprecipitation (RIP). The RNA precipitated with the studied protein can be detected by real-time polymerase chain reaction (PCR), microarray or sequencing.

Evidence for the role of transcription factors in the co-transcriptional regulation of intron retention.

Background: Alternative splicing is a widespread regulatory phenomenon that enables a single gene to produce multiple transcripts. Among the different types of alternative splicing, intron retention is one of the least explored despite its high prevalence in both plants and animals. The recent discovery that the majority of splicing is co-transcriptional has led to the finding that chromatin state affects alternative splicing.

Phenology-based adjustments improve population estimates of Antarctic breeding seabirds: the case of Cape petrels in East Antarctica.

To monitor and conserve a species, it is crucial to understand the size and distribution of populations. For seabirds, population surveys are usually conducted at peak breeding attendance. One of the largest populations of Cape petrels in East Antarctica is at the Vestfold Islands, where environmental and logistical constraints often prevent access to breeding sites at the optimal time for population surveys.

KDM3A regulates alternative splicing of cell-cycle genes following DNA damage.

Changes in the cellular environment result in chromatin structure alteration, which in turn regulates gene expression. To learn about the effect of the cellular environment on the transcriptome, we studied the H3K9 demethylase KDM3A. Using RNA-seq, we found that KDM3A regulates the transcription and alternative splicing of genes associated with cell cycle and DNA damage.

VEGFA's distal enhancer regulates its alternative splicing in CML.

Enhancer demethylation in leukemia has been shown to lead to overexpression of genes which promote cancer characteristics. The vascular endothelial growth factor A (VEGFA) enhancer, located 157 Kb downstream of its promoter, is demethylated in chronic myeloid leukemia (CML). VEGFA has several alternative splicing isoforms with different roles in cancer progression.

CBR regulates soluble leptin receptor levels via CHOP, contributing to hepatic leptin resistance.

The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity. Its reduced levels in diet-induced obesity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the endocannabinoid (eCB)/CBR system. Here we show that pharmacological activation/blockade and genetic overexpression/deletion of hepatic CBR modulates sOb-R levels and hepatic leptin resistance.

Splicing to Keep Cycling: The Importance of Pre-mRNA Splicing during the Cell Cycle.

Pre-mRNA splicing is a fundamental process in mammalian gene expression, and alternative splicing plays an extensive role in generating protein diversity. Because the majority of genes undergo pre-mRNA splicing, most cellular processes depend on proper spliceosome function. We focus on the cell cycle and describe its dependence on pre-mRNA splicing and accurate alternative splicing.

JMJD6 Regulates Splicing of Its Own Gene Resulting in Alternatively Spliced Isoforms with Different Nuclear Targets.

Jumonji-domain-containing protein 6 (JMJD6) is a Fe(II) and 2-oxogluterate (2OG) dependent oxygenase involved in gene regulation through post-translationally modifying nuclear proteins. It is highly expressed in many cancer types and linked to tumor progression and metastasis. Four alternatively-spliced transcripts were annotated.

Splicing Factor Transcript Abundance in Saliva as a Diagnostic Tool for Breast Cancer.

Breast cancer is the second leading cause of death in women above 60 years in the US. Screening mammography is recommended for women above 50 years; however, 22% of breast cancer cases are diagnosed in women below this age. We set out to develop a test based on the detection of cell-free RNA from saliva.

Large-scale implementation of pooled RNA extraction and RT-PCR for SARS-CoV-2 detection.

Introduction: Testing for active SARS-CoV-2 infection is a fundamental tool in the public health measures taken to control the COVID-19 pandemic. Because of the overwhelming use of SARS-CoV-2 reverse transcription (RT)-PCR tests worldwide, the availability of test kits has become a major bottleneck and the need to increase testing throughput is rising. We aim to overcome these challenges by pooling samples together, and performing RNA extraction and RT-PCR in pools.

Regulation of alternative splicing by p300-mediated acetylation of splicing factors.

Splicing of precursor mRNA (pre-mRNA) is an important regulatory step in gene expression. Recent evidence points to a regulatory role of chromatin-related proteins in alternative splicing regulation. Using an unbiased approach, we have identified the acetyltransferase p300 as a key chromatin-related regulator of alternative splicing.

Using accelerometers to develop time-energy budgets of wild fur seals from captive surrogates.

Background: Accurate time-energy budgets summarise an animal's energy expenditure in a given environment, and are potentially a sensitive indicator of how an animal responds to changing resources. Deriving accurate time-energy budgets requires an estimate of time spent in different activities and of the energetic cost of that activity. Bio-loggers (e.

Protein arginine methylation: a prominent modification and its demethylation.

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues.

Small Molecule Modulators of Pre-mRNA Splicing in Cancer Therapy.

Pre-mRNA splicing is a fundamental process in mammalian gene expression and alternative RNA splicing plays a considerable role in generating protein diversity. RNA splicing events are also key to the pathology of numerous diseases, particularly cancers. Some tumors are molecularly addicted to specific RNA splicing isoforms making interference with pre-mRNA processing a viable therapeutic strategy.

Carry-over body mass effect from winter to breeding in a resident seabird, the little penguin.

Using body mass and breeding data of individual penguins collected continuously over 7 years (2002-2008), we examined carry-over effects of winter body mass on timing of laying and breeding success in a resident seabird, the little penguin (Eudyptula minor). The austral winter month of July consistently had the lowest rate of colony attendance, which confirmed our expectation that penguins work hard to find resources at this time between breeding seasons. Contrary to our expectation, body mass in winter (July) was equal or higher than in the period before ('moult-recovery') and after ('pre-breeding') in 5 of 7 years for males and in all 7 years for females.

Inhibition of vemurafenib-resistant melanoma by interference with pre-mRNA splicing.

Mutations in the serine/threonine kinase BRAF are found in more than 60% of melanomas. The most prevalent melanoma mutation is BRAF(V600E), which constitutively activates downstream MAPK signalling. Vemurafenib is a potent RAF kinase inhibitor with remarkable clinical activity in BRAF(V600E)-positive melanoma tumours.