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  1. Glial cells maintain synapses by inhibiting an activity-dependent retrograde protease signal.

    PLoS genetics · 2019 · 15(3): e1007948

    Glial cells regulate multiple aspects of synaptogenesis. In the absence of Schwann cells, a peripheral glial cell, motor neurons initially innervate muscle but then degenerate. Here, using a genetic approach, we show that neural activity-regulated negative factors produced by muscle …

    PMID 30870413 DOI ↗

  2. Allele-specific binding of RNA-binding proteins reveals functional genetic variants in the RNA.

    Nature communications · 2019 · 10(1): 1338

    Allele-specific protein-RNA binding is an essential aspect that may reveal functional genetic variants (GVs) mediating post-transcriptional regulation. Recently, genome-wide detection of in vivo binding of RNA-binding proteins is greatly facilitated by the enhanced crosslinking and immunoprecipitation (eCLIP) method. We developed …

    PMID 30902979 DOI ↗

  3. RBP-Maps enables robust generation of splicing regulatory maps.

    RNA (New York, N.Y.) · 2019 · 25(2): 193-204

    Alternative splicing of pre-messenger RNA transcripts enables the generation of multiple protein isoforms from the same gene locus, providing a major source of protein diversity in mammalian genomes. RNA binding proteins (RBPs) bind to RNA to control splice site choice …

    PMID 30413564 DOI ↗

  4. Overriding FUS autoregulation in mice triggers gain-of-toxic dysfunctions in RNA metabolism and autophagy-lysosome axis.

    eLife · 2019 · 8

    Mutations in coding and non-coding regions of FUS cause amyotrophic lateral sclerosis (ALS). The latter mutations may exert toxicity by increasing FUS accumulation. We show here that broad expression within the nervous system of wild-type or either of two ALS-linked …

    PMID 30747709 DOI ↗

  5. Widespread RNA editing dysregulation in brains from autistic individuals.

    Nature neuroscience · 2019 · 22(1): 25-36

    Transcriptomic analyses of postmortem brains have begun to elucidate molecular abnormalities in autism spectrum disorder (ASD). However, a crucial pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled global patterns …

    PMID 30559470 DOI ↗

  6. A Transcriptome-wide Translational Program Defined by LIN28B Expression Level.

    Molecular cell · 2019 · 73(2): 304-313.e3

    LIN28 RNA binding proteins are dynamically expressed throughout mammalian development and during disease. However, it remains unclear how changes in LIN28 expression define patterns of post-transcriptional gene regulation. Here we show that LIN28 expression level is a key variable that …

    PMID 30527666 DOI ↗

  7. Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells.

    Frontiers in molecular neuroscience · 2018 · 11: 261

    The human brain is composed of a complex assembly of about 171 billion heterogeneous cellular units (86 billion neurons and 85 billion non-neuronal glia cells). A comprehensive description of brain cells is necessary to understand the nervous system in health …

    PMID 30147644 DOI ↗

  8. Transcriptome-pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS.

    Acta neuropathologica · 2018 · 136(3): 405-423

    Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched …

    PMID 29881994 DOI ↗

  9. An important class of intron retention events in human erythroblasts is regulated by cryptic exons proposed to function as splicing decoys.

    RNA (New York, N.Y.) · 2018 · 24(9): 1255-1265

    During terminal erythropoiesis, the splicing machinery in differentiating erythroblasts executes a robust intron retention (IR) program that impacts expression of hundreds of genes. We studied IR mechanisms in the <i>SF3B1</i> splicing factor gene, which expresses ∼50% of its transcripts in …

    PMID 29959282 DOI ↗

  10. Tissue-selective restriction of RNA editing of CaV1.3 by splicing factor SRSF9.

    Nucleic acids research · 2018 · 46(14): 7323-7338

    Adenosine DeAminases acting on RNA (ADAR) catalyzes adenosine-to-inosine (A-to-I) conversion within RNA duplex structures. While A-to-I editing is often dynamically regulated in a spatial-temporal manner, the mechanisms underlying its tissue-selective restriction remain elusive. We have previously reported that transcripts of …

    PMID 29733375 DOI ↗

  11. Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson's Disease.

    Cell stem cell · 2018 · 23(1): 123-131.e6

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain neurons (MBNs). Recent evidence suggests contribution of the adaptive immune system in PD. Here, we show a role for human T lymphocytes as cell death inducers …

    PMID 29979986 DOI ↗

  12. Sequence, Structure, and Context Preferences of Human RNA Binding Proteins.

    Molecular cell · 2018 · 70(5): 854-867.e9

    RNA binding proteins (RBPs) orchestrate the production, processing, and function of mRNAs. Here, we present the affinity landscapes of 78 human RBPs using an unbiased assay that determines the sequence, structure, and context preferences of these proteins in vitro by …

    PMID 29883606 DOI ↗

  13. Systematic Discovery of RNA Binding Proteins that Regulate MicroRNA Levels.

    Molecular cell · 2018 · 69(6): 1005-1016.e7

    RNA binding proteins (RBPs) interact with primary, precursor, and mature microRNAs (miRs) to influence mature miR levels, which in turn affect critical aspects of human development and disease. To understand how RBPs contribute to miR biogenesis, we analyzed human enhanced …

    PMID 29547715 DOI ↗

  14. Advances and challenges in the detection of transcriptome-wide protein-RNA interactions.

    Wiley interdisciplinary reviews. RNA · 2018 · 9(1)

    RNA binding proteins (RBPs) play key roles in determining cellular behavior by manipulating the processing of target RNAs. Robust methods are required to detect the numerous binding sites of RBPs across the transcriptome. RNA-immunoprecipitation followed by sequencing (RIP-seq) and crosslinking …

    PMID 28853213 DOI ↗

  15. Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules.

    Cell · 2018 · 172(3): 590-604.e13

    Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, …

    PMID 29373831 DOI ↗

  16. Self-Transfecting Micellar RNA: Modulating Nanoparticle Cell Interactions via High Density Display of Small Molecule Ligands on Micelle Coronas.

    Bioconjugate chemistry · 2018 · 29(1): 126-135

    The intracellular delivery of synthetic nucleic acids represents a major challenge in biotechnology and in biomedicine. Methods to deliver short, double-stranded RNA to living cells are of particular interest because of the potential to engage the RNA interference machinery and …

    PMID 29286237 DOI ↗

  17. Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end Enhanced Crosslinking and Immunoprecipitation (seCLIP).

    Methods in molecular biology (Clifton, N.J.) · 2017 · 1648: 177-200

    Profiling of RNA binding protein targets in vivo provides critical insights into the mechanistic roles they play in regulating RNA processing. The enhanced crosslinking and immunoprecipitation (eCLIP) methodology provides a framework for robust, reproducible identification of transcriptome-wide protein-RNA interactions, with …

    PMID 28766298 DOI ↗

  18. Erratum to: Robust, Cost-Effective Profiling of RNA Binding Protein Targets with Single-end Enhanced Crosslinking and Immunoprecipitation (seCLIP).

    Methods in molecular biology (Clifton, N.J.) · 2017 · 1648: E1

    PMID 29230720 DOI ↗

  19. Short poly(A) tails are a conserved feature of highly expressed genes.

    Nature structural & molecular biology · 2017 · 24(12): 1057-1063

    Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to …

    PMID 29106412 DOI ↗

  20. Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA metabolism.

    Nucleic acids research · 2017 · 45(21): 12509-12528

    To counteract the breakdown of genome integrity, eukaryotic cells have developed a network of surveillance pathways to prevent and resolve DNA damage. Recent data has recognized the importance of RNA binding proteins (RBPs) in DNA damage repair (DDR) pathways. Here, …

    PMID 29069457 DOI ↗

  21. NEAT1 scaffolds RNA-binding proteins and the Microprocessor to globally enhance pri-miRNA processing.

    Nature structural & molecular biology · 2017 · 24(10): 816-824

    MicroRNA (miRNA) biogenesis is known to be modulated by a variety of RNA-binding proteins (RBPs), but in most cases, individual RBPs appear to influence the processing of a small subset of target miRNAs. Here, we report that the RNA-binding NONO-PSF …

    PMID 28846091 DOI ↗

  22. Genetic mutations in RNA-binding proteins and their roles in ALS.

    Human genetics · 2017 · 136(9): 1193-1214

    Mutations in genes that encode RNA-binding proteins (RBPs) have emerged as critical determinants of neurological diseases, especially motor neuron disorders such as amyotrophic lateral sclerosis (ALS). RBPs are involved in all aspects of RNA processing, controlling the life cycle of …

    PMID 28762175 DOI ↗

  23. The <i>C. elegans</i> neural editome reveals an ADAR target mRNA required for proper chemotaxis.

    eLife · 2017 · 6

    ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. <i>Caenorhabditis elegans</i> lacking ADARs exhibit …

    PMID 28925356 DOI ↗

  24. Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9.

    Cell · 2017 · 170(5): 899-912.e10

    Microsatellite repeat expansions in DNA produce pathogenic RNA species that cause dominantly inherited diseases such as myotonic dystrophy type 1 and 2 (DM1/2), Huntington's disease, and C9orf72-linked amyotrophic lateral sclerosis (C9-ALS). Means to target these repetitive RNAs are required for …

    PMID 28803727 DOI ↗

  25. Variation in single-nucleotide sensitivity of eCLIP derived from reverse transcription conditions.

    Methods (San Diego, Calif.) · 2017 · 126: 29-37

    Crosslinking and immunoprecipitation (CLIP) followed by high-throughput sequencing identifies the binding sites of RNA binding proteins on RNAs. The covalent RNA-amino acid adducts produced by UV irradiation can cause premature reverse transcription termination and deletions (referred to as crosslink-induced mutation …

    PMID 28790018 DOI ↗