- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Cancer-related molecular mechanisms research
- Amino Acid Enzymes and Metabolism
- Molecular Biology Techniques and Applications
- Hematopoietic Stem Cell Transplantation
- interferon and immune responses
- Systemic Lupus Erythematosus Research
- Evolution and Genetic Dynamics
- Prion Diseases and Protein Misfolding
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Mesenchymal stem cell research
- Genetic Neurodegenerative Diseases
- MicroRNA in disease regulation
- Endoplasmic Reticulum Stress and Disease
- Congenital heart defects research
Blaze Bioscience (United States)
2024-2025
University of California, San Diego
2013-2022
Sanford Consortium for Regenerative Medicine
2015-2016
Center for Genomic Science
2015
University of Washington
2011-2012
RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present affinity landscapes 78 human RBPs using an unbiased assay that determines sequence, structure, context preferences these in vitro by deep sequencing bound RNAs. These data enable construction "RNA maps" RBP activity without requiring crosslinking-based assays. We found unexpectedly low diversity motifs, implying frequent convergence specificity toward a relatively small set many with...
An Aluring new autoantibody target Autoimmunity is the immune system's ultimate act of betrayal. Cells designed to protect against invading microbes suddenly host instead. In autoimmune disease systemic lupus erythematosus, antibodies DNA and proteins, including RNA binding protein Ro60. Hung et al. discovered that Ro60 bound endogenous Alu retroelements. They detected antibody-Ro60-Alu complexes in blood individuals with an enrichment transcripts. probably primes RNA-binding innate...
A critical step in uncovering rules of RNA processing is to study the vivo regulatory networks binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges large-scale analysis across datasets. The development enhanced CLIP (eCLIP) enabled for 150 RBPs K562 HepG2, creating a unique resource interactomes profiled with standardized methodology same cell types.
Abstract The RNA-binding protein (RBP) TAF15 is implicated in amyotrophic lateral sclerosis (ALS). To compare function to that of two ALS-associated RBPs, FUS and TDP-43, we integrate CLIP-seq RNA Bind-N-Seq technologies, show binds ∼4,900 RNAs enriched for GGUA motifs adult mouse brains. exhibit similar binding patterns introns, are 3′ untranslated regions alter genes distinct from TDP-43. However, unlike has a minimal role alternative splicing. In human neural progenitors, affect turnover...
Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using enhanced UV crosslinking immunoprecipitation (eCLIP), we identify targets the IMP/IGF2BP family RNA-binding proteins in hPSCs. At broad region binding site levels, IMP1 IMP2 show reproducible a large overlapping set 3' UTR-enriched targets. Bind-N-seq applied recombinant full-length reveals CA-rich motifs that are enriched eCLIP-defined sites. We...
Abstract Genomes encompass all the information necessary to specify development and function of an organism. In addition genes, genomes also contain a myriad functional elements that control various steps in gene expression. A major class these only when transcribed into RNA as they serve binding sites for proteins (RBPs), which act post-transcriptional processes including splicing, cleavage polyadenylation, editing, localization, stability, translation. Despite importance encoded genome,...
Mitochondrial genomes co-evolve with the nuclear genome over evolutionary timescales and are shaped by selection in female germline. Here we investigate how mismatching between mitochondrial ancestry impacts somatic evolution of different tissues throughout ageing. We used ultrasensitive duplex sequencing to profile ~2.5 million across five haplotypes three young aged mice, cataloguing ~1.2 ultralow-frequency inherited mutations, which 81,097 unique. identify haplotype-specific mutational...
Alternative splicing of pre-messenger RNA transcripts enables the generation multiple protein isoforms from same gene locus, providing a major source diversity in mammalian genomes. binding proteins (RBPs) bind to control splice site choice and define which exons are included resulting mature transcript. However, depending on where RBPs relative sites, they can activate or repress usage. To explore this position-specific regulation, vivo sites identified by methods such as cross-linking...
Crosslinking and immunoprecipitation (CLIP) followed by high-throughput sequencing identifies the binding sites of RNA proteins on RNAs. The covalent RNA-amino acid adducts produced UV irradiation can cause premature reverse transcription termination deletions (referred to as crosslink-induced mutation (CIMS)), which may decrease overall cDNA yield but are exploited in state-of-the-art CLIP methods identify these crosslink at single-nucleotide resolution. Here, we show ratio both crosslinked...