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320 results
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Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.
Nature · 2016 · 532(7600): 508-511
Umbilical cord blood-derived haematopoietic stem cells (HSCs) are essential for many life-saving regenerative therapies. However, despite their advantages for transplantation, their clinical use is restricted because HSCs in cord blood are found only in small numbers. Small molecules that enhance …
PMID 27121842 DOI ↗
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Enhanced CLIP Uncovers IMP Protein-RNA Targets in Human Pluripotent Stem Cells Important for Cell Adhesion and Survival.
Cell reports · 2016 · 15(3): 666-679
Human pluripotent stem cells (hPSCs) require precise control of post-transcriptional RNA networks to maintain proliferation and survival. Using enhanced UV crosslinking and immunoprecipitation (eCLIP), we identify RNA targets of the IMP/IGF2BP family of RNA-binding proteins in hPSCs. At the broad …
PMID 27068461 DOI ↗
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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 ↗
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A Small RNA-Catalytic Argonaute Pathway Tunes Germline Transcript Levels to Ensure Embryonic Divisions.
Cell · 2016 · 165(2): 396-409
Multiple division cycles without growth are a characteristic feature of early embryogenesis. The female germline loads proteins and RNAs into oocytes to support these divisions, which lack many quality control mechanisms operating in somatic cells undergoing growth. Here, we describe …
PMID 27020753 DOI ↗
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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 ↗
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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 ↗
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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 ↗
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The Clothes Make the mRNA: Past and Present Trends in mRNP Fashion.
Annual review of biochemistry · 2015 · 84: 325-54
Throughout their lifetimes, messenger RNAs (mRNAs) associate with proteins to form ribonucleoproteins (mRNPs). Since the discovery of the first mRNP component more than 40 years ago, what is known as the mRNA interactome now comprises >1,000 proteins. These proteins bind …
PMID 25784054 DOI ↗
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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 ↗
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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 ↗
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Reply to: "CD8(+) T cell diversification by asymmetric cell division".
Nature immunology · 2015 · 16(9): 893-4
PMID 26287585 DOI ↗
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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 ↗
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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 ↗
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Nxf1 natural variant E610G is a semi-dominant suppressor of IAP-induced RNA processing defects.
PLoS genetics · 2015 · 11(4): e1005123
Endogenous retroviruses and retrotransposons contribute functional genetic variation in animal genomes. In mice, Intracisternal A Particles (IAPs) are a frequent source of both new mutations and polymorphism across laboratory strains. Intronic IAPs can induce alternative RNA processing choices, including alternative …
PMID 25835743 DOI ↗
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RNA-binding proteins in neurodegeneration: Seq and you shall receive.
Trends in neurosciences · 2015 · 38(4): 226-36
As critical players in gene regulation, RNA binding proteins (RBPs) are taking center stage in our understanding of cellular function and disease. In our era of bench-top sequencers and unprecedented computational power, biological questions can be addressed in a systematic, …
PMID 25765321 DOI ↗
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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 ↗
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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 ↗
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ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP.
Nature communications · 2015 · 6: 6171
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their …
PMID 25625564 DOI ↗
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Preface.
Advances in experimental medicine and biology · 2014 · 825: v - vii
PMID 25453141
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A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.
PloS one · 2014 · 9(12): e113258
The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe …
PMID 25474699 DOI ↗
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Preface.
Advances in experimental medicine and biology · 2014 · 825: v - vii
PMID 25513200
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The Period protein homolog LIN-42 negatively regulates microRNA biogenesis in C. elegans.
Developmental biology · 2014 · 390(2): 126-35
MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate gene expression in many multicellular organisms. They are encoded in the genome and transcribed into primary (pri-) miRNAs before two processing steps that ultimately produce the mature miRNA. In order to generate …
PMID 24699545 DOI ↗
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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 ↗
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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 ↗
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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 ↗