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Programmable RNA Tracking in Live Cells with CRISPR/Cas9.

Cell · 2016 · 165(2): 488-96

RNA-programmed genome editing using CRISPR/Cas9 from Streptococcus pyogenes has enabled rapid and accessible alteration of specific genomic loci in many organisms. A flexible means to target RNA would allow alteration and imaging of endogenous RNA transcripts analogous to CRISPR/Cas-based genomic …

PMID 26997482 DOI ↗

Resources for the Comprehensive Discovery of Functional RNA Elements.

Molecular cell · 2016 · 61(6): 903-13

Transcriptome-wide maps of RNA binding protein (RBP)-RNA interactions by immunoprecipitation (IP)-based methods such as RNA IP (RIP) and crosslinking and IP (CLIP) are key starting points for evaluating the molecular roles of the thousands of human RBPs. A significant bottleneck …

PMID 26990993 DOI ↗

PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.

Nature medicine · 2016 · 22(1): 37-45

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT …

PMID 26642438 DOI ↗

Blurred Boundaries: The RNA Binding Protein Lin28A Is Also an Epigenetic Regulator.

Molecular cell · 2016 · 61(1): 1-2

Lin28A is best known as a post-transcriptional regulator of gene expression. In this issue, Zeng et al. (2016) show that Lin28A has an unexpected role as an epigenetic regulator of DNA.

PMID 26748607 DOI ↗

The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.

Science (New York, N.Y.) · 2015 · 350(6259): 455-9

Autoantibodies target the RNA binding protein Ro60 in systemic lupus erythematosus (SLE) and Sjögren's syndrome. However, it is unclear whether Ro60 and its associated RNAs contribute to disease pathogenesis. We catalogued the Ro60-associated RNAs in human cell lines and found …

PMID 26382853 DOI ↗

A Gene Regulatory Network Cooperatively Controlled by Pdx1 and Sox9 Governs Lineage Allocation of Foregut Progenitor Cells.

Cell reports · 2015 · 13(2): 326-36

The generation of pancreas, liver, and intestine from a common pool of progenitors in the foregut endoderm requires the establishment of organ boundaries. How dorsal foregut progenitors activate pancreatic genes and evade the intestinal lineage choice remains unclear. Here, we …

PMID 26440894 DOI ↗

Reply to: "CD8(+) T cell diversification by asymmetric cell division".

Nature immunology · 2015 · 16(9): 893-4

PMID 26287585 DOI ↗

Target Discrimination in Nonsense-Mediated mRNA Decay Requires Upf1 ATPase Activity.

Molecular cell · 2015 · 59(3): 413-25

RNA quality-control pathways get rid of faulty RNAs and therefore must be able to discriminate these RNAs from those that are normal. Here we present evidence that the adenosine triphosphatase (ATPase) cycle of the SF1 helicase Upf1 is required for …

PMID 26253027 DOI ↗

Applications of Cas9 as an RNA-programmed RNA-binding protein.

BioEssays : news and reviews in molecular, cellular and developmental biology · 2015 · 37(7): 732-9

The Streptococcus pyogenes CRISPR-Cas system has gained widespread application as a genome editing and gene regulation tool as simultaneous cellular delivery of the Cas9 protein and guide RNAs enables recognition of specific DNA sequences. The recent discovery that Cas9 can …

PMID 25880497 DOI ↗

Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.

Circulation · 2015 · 131(14): 1278-1290

Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators with important functions in development and disease. Here, we sought to identify and functionally characterize novel lncRNAs critical for vertebrate development. By relying on human pluripotent stem cell differentiation models, …

PMID 25739401 DOI ↗

Regulation of asymmetric division and CD8+ T lymphocyte fate specification by protein kinase Cζ and protein kinase Cλ/ι.

Journal of immunology (Baltimore, Md. : 1950) · 2015 · 194(5): 2249-59

During an immune response against a microbial pathogen, activated naive T lymphocytes give rise to effector cells that provide acute host defense and memory cells that provide long-lived immunity. It has been shown that T lymphocytes can undergo asymmetric division, …

PMID 25617472 DOI ↗

Intracellular mRNA regulation with self-assembled locked nucleic acid polymer nanoparticles.

Journal of the American Chemical Society · 2014 · 136(21): 7615-8

We present an untemplated, single-component antisense oligonucleotide delivery system capable of regulating mRNA abundance in live human cells. While most approaches to nucleic acid delivery rely on secondary carriers and complex multicomponent charge-neutralizing formulations, we demonstrate efficient delivery using a …

PMID 24827740 DOI ↗

Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses.

Nature immunology · 2014 · 15(4): 365-372

T lymphocytes responding to microbial infection give rise to effector cells that mediate acute host defense and memory cells that provide long-lived immunity, but the fundamental question of when and how these cells arise remains unresolved. Here we combined single-cell …

PMID 24584088 DOI ↗

Human cytomegalovirus infection of human embryonic stem cell-derived primitive neural stem cells is restricted at several steps but leads to the persistence of viral DNA.

Journal of virology · 2014 · 88(8): 4021-39

Congenital human cytomegalovirus (HCMV) infection is a major cause of central nervous system structural anomalies and sensory impairments. It is likely that the stage of fetal development, as well as the state of differentiation of susceptible cells at the time …

PMID 24453373 DOI ↗

The dsRBP and inactive editor ADR-1 utilizes dsRNA binding to regulate A-to-I RNA editing across the C. elegans transcriptome.

Cell reports · 2014 · 6(4): 599-607

Inadequate adenosine-to-inosine editing of noncoding regions occurs in disease but is often uncorrelated with ADAR levels, underscoring the need to study deaminase-independent control of editing. C. elegans have two ADAR proteins, ADR-2 and the theoretically catalytically inactive ADR-1. Using high-throughput …

PMID 24508457 DOI ↗

Functional genomic analysis of the let-7 regulatory network in Caenorhabditis elegans.

PLoS genetics · 2013 · 9(3): e1003353

The let-7 microRNA (miRNA) regulates cellular differentiation across many animal species. Loss of let-7 activity causes abnormal development in Caenorhabditis elegans and unchecked cellular proliferation in human cells, which contributes to tumorigenesis. These defects are due to improper expression of …

PMID 23516374 DOI ↗

Differential L1 regulation in pluripotent stem cells of humans and apes.

Nature · 2013 · 503(7477): 525-529

Identifying cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic understanding of the evolution and diversity of our own species. Until now, preserved tissues have been the main source for most comparative studies between …

PMID 24153179 DOI ↗

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration.

Proceedings of the National Academy of Sciences of the United States of America · 2013 · 110(47): E4530-9

Expanded hexanucleotide repeats in the chromosome 9 open reading frame 72 (C9orf72) gene are the most common genetic cause of ALS and frontotemporal degeneration (FTD). Here, we identify nuclear RNA foci containing the hexanucleotide expansion (GGGGCC) in patient cells, including …

PMID 24170860 DOI ↗

Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment.

Genes & development · 2013 · 27(21): 2332-44

A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem cell …

PMID 24186978 DOI ↗

Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing.

Molecular cell · 2013 · 50(2): 223-35

SR proteins are well-characterized RNA binding proteins that promote exon inclusion by binding to exonic splicing enhancers (ESEs). However, it has been unclear whether regulatory rules deduced on model genes apply generally to activities of SR proteins in the cell. …

PMID 23562324 DOI ↗

ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.

Proceedings of the National Academy of Sciences of the United States of America · 2013 · 110(8): E736-45

Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, …

PMID 23382207 DOI ↗

Divergent roles of ALS-linked proteins FUS/TLS and TDP-43 intersect in processing long pre-mRNAs.

Nature neuroscience · 2012 · 15(11): 1488-97

FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. We found that FUS/TLS binds to RNAs from >5,500 genes in mouse and human brain, primarily through a GUGGU-binding motif. We …

PMID 23023293 DOI ↗

LIN28 binds messenger RNAs at GGAGA motifs and regulates splicing factor abundance.

Molecular cell · 2012 · 48(2): 195-206

LIN28 is a conserved RNA-binding protein implicated in pluripotency, reprogramming, and oncogenesis. It was previously shown to act primarily by blocking let-7 microRNA (miRNA) biogenesis, but here we elucidate distinct roles of LIN28 regulation via its direct messenger RNA (mRNA) …

PMID 22959275 DOI ↗

Retrotransposon long interspersed nucleotide element-1 (LINE-1) is activated during salamander limb regeneration.

Development, growth & differentiation · 2012 · 54(7): 673-85

Salamanders possess an extraordinary capacity for tissue and organ regeneration when compared to mammals. In our effort to characterize the unique transcriptional fingerprint emerging during the early phase of salamander limb regeneration, we identified transcriptional activation of some germline-specific genes …

PMID 22913491 DOI ↗

Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome.

Human molecular genetics · 2012 · 21(17): 3825-34

Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA …

PMID 22661500 DOI ↗