A5010146665- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
- Chromosomal and Genetic Variations
- Viral Infections and Immunology Research
- Cancer Mechanisms and Therapy
- Animal Behavior and Reproduction
- Viral Infectious Diseases and Gene Expression in Insects
- Genomic variations and chromosomal abnormalities
- Insect and Arachnid Ecology and Behavior
- Cancer-related molecular mechanisms research
- RNA Interference and Gene Delivery
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Neurobiology and Insect Physiology Research
- Birth, Development, and Health
- Genomics and Phylogenetic Studies
- Renin-Angiotensin System Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
Dovetail Genomics (United States)
2013-2024
Stowers Institute for Medical Research
2009-2019
University of Kansas Medical Center
2011-2014
University of California, Berkeley
2002-2011
University of California, San Francisco
2010
University Medical Center
2010
University of Kansas
2010
Innovative Genomics Institute
2009
Université de Sherbrooke
1997-2002
Long-range and highly accurate de novo assembly from short-read data is one of the most pressing challenges in genomics. Recently, it has been shown that read pairs generated by proximity ligation DNA chromatin living tissue can address this problem, dramatically increasing scaffold contiguity assemblies. Here, we describe a simpler approach (“Chicago”) based on vitro reconstituted chromatin. We two Chicago sets with human developed statistical model new software pipeline (“HiRise”) identify...
Abstract The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling 1 and is altered over 20% of cancers 2,3 . Here we developed proteolysis-targeting chimera (PROTAC) degrader the SWI/SNF ATPase subunits, SMARCA2 SMARCA4, called AU-15330. Androgen receptor (AR) + forkhead box A1 (FOXA1) prostate cancer cells are exquisitely sensitive to dual SMARCA4 degradation relative normal other cell lines. rapidly compacts cis -regulatory elements bound by...
Abstract We have recently shown that a third of reliably-inferred alternative mRNA isoforms are candidates for nonsense-mediated decay (NMD), an surveillance system (Lewis et al., 2003; Proc. Natl Acad. Sci. USA, 100, 189–192). Rather than being translated to yield protein, these transcripts expected be degraded and may subject regulated unproductive splicing translation (RUST). Our initial experimental studies consistent with predictions suggest unappreciated role NMD in several human...
SR proteins are a well-conserved class of RNA-binding that essential for regulation splice-site selection, and have also been implicated as key regulators during other stages RNA metabolism. For many proteins, the complexity targets specificity location poorly understood. It is unclear if general rules governing protein alternative pre-mRNA splicing (AS) uncovered individual on few model genes, apply to activity all endogenous targets. Using RNA-seq, we characterize global AS eight...
To gain insight into splicing regulation, we developed a microarray to assay all annotated alternative events in Drosophila melanogaster and identified the splice controlled by four regulators: dASF/SF2, B52/SRp55, hrp48, PSI. The number of each these factors was found be highly variable: dASF/SF2 strongly affects >300 events, whereas PSI only 43 events. Pairwise analysis also revealed many instances site usage affected multiple provides framework understand network controlling...
Transcription and pre-mRNA alternative splicing are highly regulated processes that play major roles in modulating eukaryotic gene expression. It is increasingly apparent other pathways of RNA metabolism, including small biogenesis, can regulate these processes. However, a direct link between has remained elusive. Here we show the pathway protein Argonaute-2 (Ago-2) regulates patterns specific transcripts Drosophila nucleus using genome-wide methods conjunction with RNAi cell culture Ago-2...
The hnRNP A1 pre-mRNA is alternatively spliced to yield the and A1b mRNAs, which encode proteins differing in their ability modulate 5′ splice site selection. Sequencing a genomic portion of murine gene revealed that intron separating exon 7 alternative 7B highly conserved between mouse human. In vitro splicing assays indicate element (CE1) from central shifts selection toward distal donor when positioned sites 7B. vivo, CE1 promotes skipping. A 17-nucleotide sequence within (CE1a)...
Alternative mRNA splicing adds a layer of regulation to the expression thousands genes in Drosophila melanogaster. Not all alternative results functional protein; it can also yield isoforms with premature stop codons that are degraded by nonsense-mediated decay (NMD) pathway. This coupling and NMD provides mechanism for gene is highly conserved mammals. active Drosophila, but its effect on repertoire splice forms has been unknown, as which recognizes targets. Here, we have employed custom...
FACT (facilitates chromatin transcription) is an evolutionarily conserved histone chaperone that was initially identified as activity capable of promoting RNA polymerase II (Pol II) transcription through nucleosomes in vitro. In this report, we describe a global analysis function Pol Drosophila. We present evidence loss has dramatic impact on elongation-coupled processes including H3 lysine 4 (H3K4) and H3K36 methylation, consistent with role for coordinating modification architecture during...
In the heterogeneous nuclear ribonucleoprotein (hnRNP) A1 pre-mRNA, different regions in introns flanking alternative exon 7B have been implicated production of and A1B mRNA splice isoforms. Among these, CE1a CE4 elements, located downstream common 7 7B, respectively, are bound by hnRNP to promote skipping 7Bin vivo distal 5′ site selection vitro. Here, we report that is flanked an additional high affinity binding (CE1d). a manner similar CE1a, CE1d affects Consistent with role for activity...
AbstractComplex functional coupling exists between transcriptional elongation and pre-mRNA alternative splicing. Pausing sites changes in the rate of transcription by RNA polymerase II (RNAPII) may therefore have fundamental impacts regulation Here, we show that splicing-related factor TCERG1 regulates splicing apoptosis gene Bcl-x a promoter-dependent manner. promotes short isoform (Bcl-xs) through SB1 regulatory element located first half exon 2. Consistent with these results, associates...
We recently identified the 4-pyridinone-benzisothiazole carboxamide compound 1C8 as displaying strong anti-HIV-1 potency against a variety of clinical strains in vitro. Here we show that decreases expression HIV-1 and alters splicing events involved production mRNAs. Although was designed to be structural mimic fused tetracyclic indole IDC16 targets SRSF1, it did not affect splice site shifting activity SRSF1. Instead, altered regulation mediated by SRSF10. Depleting SRSF10 RNA interference...
Abstract Alternative Lengthening of Telomeres (ALT) is an aberrant DNA recombination pathway which grants replicative immortality to approximately 10% all cancers. Despite this high prevalence ALT in cancer, the mechanism and genetics by cells activate remain incompletely understood. A major challenge dissecting events that initiate extremely low frequency induction human cell systems. Guided genetic lesions have been associated with from cancer sequencing studies, we genetically engineered...
Despite the prevalence and biological relevance of both signaling pathways alternative pre-mRNA splicing, our knowledge how intracellular impacts on splicing regulation remains fragmentary. We report a genome-wide analysis using splicing-sensitive microarrays changes in induced by activation two distinct pathways, insulin wingless, Drosophila cells culture.Alternative affect more than 150 genes 50 are regulated wingless activation. About 40% showing also show mRNA levels, suggesting but...