Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.

Abstract:

:RNA transcripts are subject to posttranscriptional gene regulation involving hundreds of RNA-binding proteins (RBPs) and microRNA-containing ribonucleoprotein complexes (miRNPs) expressed in a cell-type dependent fashion. We developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs. The crosslinked sites are revealed by thymidine to cytidine transitions in the cDNAs prepared from immunopurified RNPs of 4-thiouridine-treated cells. We determined the binding sites and regulatory consequences for several intensely studied RBPs and miRNPs, including PUM2, QKI, IGF2BP1-3, AGO/EIF2C1-4 and TNRC6A-C. Our study revealed that these factors bind thousands of sites containing defined sequence motifs and have distinct preferences for exonic versus intronic or coding versus untranslated transcript regions. The precise mapping of binding sites across the transcriptome will be critical to the interpretation of the rapidly emerging data on genetic variation between individuals and how these variations contribute to complex genetic diseases.

journal_name

Cell

journal_title

Cell

authors

Hafner M,Landthaler M,Burger L,Khorshid M,Hausser J,Berninger P,Rothballer A,Ascano M Jr,Jungkamp AC,Munschauer M,Ulrich A,Wardle GS,Dewell S,Zavolan M,Tuschl T

doi

10.1016/j.cell.2010.03.009

subject

Has Abstract

pub_date

2010-04-02 00:00:00

pages

129-41

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(10)00245-X

journal_volume

141

pub_type

杂志文章

相关文献

CELL文献大全
  • The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes.

    abstract::Fertilized clam embryos synthesize several new cell-cycle-related proteins. The cloned cDNA and derived amino acid sequences of one of these, cyclin A, are presented here. Immunoblots with an anti-cyclin A antibody reveal that cyclin A is undetectable in oocytes, appears within 15 min of fertilization, and is destroye...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90801-9

    authors: Swenson KI,Farrell KM,Ruderman JV

    更新日期:1986-12-26 00:00:00

  • Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif.

    abstract::We have adopted Drosophila tissue culture cells as a host system for studying the structure and function of mammalian transcription factors. These cells provide an Sp1-deficient background and have been used in a complementation assay to identify functional domains of human transcription factor Sp1. The SV40 early pro...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(88)90144-4

    authors: Courey AJ,Tjian R

    更新日期:1988-12-02 00:00:00

  • Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism.

    abstract::NF-kappa B is a nuclear protein, found only in cells that transcribe immunoglobulin light chain genes, that interacts with a defined site in the kappa immunoglobulin enhancer. This protein can be induced in pre-B cells by stimulation with bacterial lipopolysaccharide (LPS). The induction involves a posttranslational a...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90807-x

    authors: Sen R,Baltimore D

    更新日期:1986-12-26 00:00:00

  • Chaperone activity with a redox switch.

    abstract::Hsp33, a member of a newly discovered heat shock protein family, was found to be a very potent molecular chaperone. Hsp33 is distinguished from all other known molecular chaperones by its mode of functional regulation. Its activity is redox regulated. Hsp33 is a cytoplasmically localized protein with highly reactive c...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)80547-4

    authors: Jakob U,Muse W,Eser M,Bardwell JC

    更新日期:1999-02-05 00:00:00

  • The structure of ClpB: a molecular chaperone that rescues proteins from an aggregated state.

    abstract::Molecular chaperones assist protein folding by facilitating their "forward" folding and preventing aggregation. However, once aggregates have formed, these chaperones cannot facilitate protein disaggregation. Bacterial ClpB and its eukaryotic homolog Hsp104 are essential proteins of the heat-shock response, which have...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(03)00807-9

    authors: Lee S,Sowa ME,Watanabe YH,Sigler PB,Chiu W,Yoshida M,Tsai FT

    更新日期:2003-10-17 00:00:00

  • Posttranscriptional crossregulation between Drosha and DGCR8.

    abstract::The Drosha-DGCR8 complex, also known as Microprocessor, is essential for microRNA (miRNA) maturation. Drosha functions as the catalytic subunit, while DGCR8 (also known as Pasha) recognizes the RNA substrate. Although the action mechanism of this complex has been intensively studied, it remains unclear how Drosha and ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2008.10.053

    authors: Han J,Pedersen JS,Kwon SC,Belair CD,Kim YK,Yeom KH,Yang WY,Haussler D,Blelloch R,Kim VN

    更新日期:2009-01-09 00:00:00

  • The LIM domain is a modular protein-binding interface.

    abstract::LIM domains are zinc-binding protein sequences that are found in a growing number of proteins, including certain transcriptional regulators, proto-oncogene products, and adhesion plaque constituents. Here we define the biological activity of the LIM domain through studies of an adhesion plaque protein called zyxin tha...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(94)90191-0

    authors: Schmeichel KL,Beckerle MC

    更新日期:1994-10-21 00:00:00

  • Genome-wide mapping and characterization of Notch-regulated long noncoding RNAs in acute leukemia.

    abstract::Notch signaling is a key developmental pathway that is subject to frequent genetic and epigenetic perturbations in many different human tumors. Here we investigate whether long noncoding RNA (lncRNA) genes, in addition to mRNAs, are key downstream targets of oncogenic Notch1 in human T cell acute lymphoblastic leukemi...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2014.05.049

    authors: Trimarchi T,Bilal E,Ntziachristos P,Fabbri G,Dalla-Favera R,Tsirigos A,Aifantis I

    更新日期:2014-07-31 00:00:00

  • A Mechanism for Sustained Cellulose Synthesis during Salt Stress.

    abstract::Abiotic stress, such as salinity, drought, and cold, causes detrimental yield losses for all major plant crop species. Understanding mechanisms that improve plants' ability to produce biomass, which largely is constituted by the plant cell wall, is therefore of upmost importance for agricultural activities. Cellulose ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2015.08.028

    authors: Endler A,Kesten C,Schneider R,Zhang Y,Ivakov A,Froehlich A,Funke N,Persson S

    更新日期:2015-09-10 00:00:00

  • Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells.

    abstract::We have isolated the bovine and human genes for Müllerian inhibiting substance (MIS), a testicular glycoprotein that causes regression of the Müllerian duct during development of the male embryo. The mRNA sequence of bovine MIS, determined from an analysis of cDNA and genomic clones, codes for a protein of 575 amino a...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(86)90783-x

    authors: Cate RL,Mattaliano RJ,Hession C,Tizard R,Farber NM,Cheung A,Ninfa EG,Frey AZ,Gash DJ,Chow EP

    更新日期:1986-06-06 00:00:00

  • Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm.

    abstract::Ventral midline cells at different rostrocaudal levels of the central nervous system exhibit distinct properties but share the ability to pattern the dorsoventral axis of the neural tube. We show here that ventral midline cells acquire distinct identities in response to the different signaling activities of underlying...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)80334-7

    authors: Dale JK,Vesque C,Lints TJ,Sampath TK,Furley A,Dodd J,Placzek M

    更新日期:1997-07-25 00:00:00

  • The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID.

    abstract::Drosophila Reaper (RPR), Head Involution Defective (HID), and GRIM induce caspase-dependent cell death and physically interact with the cell death inhibitor DIAP1. Here we show that HID blocks DIAP1's ability to inhibit caspase activity and provide evidence suggesting that RPR and GRIM can act similarly. Based on thes...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)81974-1

    authors: Wang SL,Hawkins CJ,Yoo SJ,Müller HA,Hay BA

    更新日期:1999-08-20 00:00:00

  • Integrin alpha8beta1 is critically important for epithelial-mesenchymal interactions during kidney morphogenesis.

    abstract::We present genetic evidence that integrins regulate epithelial-mesenchymal interactions during organogenesis. Mice with a mutation in the alpha8 gene do not express the integrin alpha8 beta1 and exhibit profound deficits in kidney morphogenesis. In wild-type animals, inductive interactions between the ureteric epithel...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)81903-0

    authors: Müller U,Wang D,Denda S,Meneses JJ,Pedersen RA,Reichardt LF

    更新日期:1997-03-07 00:00:00

  • Making Sense of Mutation: What D614G Means for the COVID-19 Pandemic Remains Unclear.

    abstract::In this issue of Cell, Korber et al. found that a SARS-CoV-2 variant in the spike protein D614G rapidly became dominant around the world. Although clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are ...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2020.06.040

    authors: Grubaugh ND,Hanage WP,Rasmussen AL

    更新日期:2020-08-20 00:00:00

  • Enhancement of memory-related long-term facilitation by ApAF, a novel transcription factor that acts downstream from both CREB1 and CREB2.

    abstract::The memory for sensitization of the gill withdrawal reflex in Aplysia is reflected in facilitation of the monosynaptic connection between the sensory and motor neurons of the reflex. The switch from short- to long-term facilitation requires activation of CREB1, derepression of ApCREB2, and induction of ApC/EBP. In sea...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)00163-x

    authors: Bartsch D,Ghirardi M,Casadio A,Giustetto M,Karl KA,Zhu H,Kandel ER

    更新日期:2000-11-10 00:00:00

  • R2D2 leads the silencing trigger to mRNA's death star.

    abstract::During RNA interference (RNAi), Dicer generates short interfering RNAs (siRNAs), which then guide target mRNA cleavage by the RISC complex. Now, Liu et al. identify R2D2, a Dicer-associated protein that is important for siRNA incorporation into RISC, thus linking the initiation and execution phases of RNAi. ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(03)00806-7

    authors: Pellino JL,Sontheimer EJ

    更新日期:2003-10-17 00:00:00

  • Sensory Neurons that Detect Stretch and Nutrients in the Digestive System.

    abstract::Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate th...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2016.05.011

    authors: Williams EK,Chang RB,Strochlic DE,Umans BD,Lowell BB,Liberles SD

    更新日期:2016-06-30 00:00:00

  • Paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila.

    abstract::The JAK/STAT signaling pathway, renowned for its effects on cell proliferation and survival, is constitutively active in various human cancers, including ovarian. We have found that JAK and STAT are required to convert the border cells in the Drosophila ovary from stationary, epithelial cells to migratory, invasive ce...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(01)00607-9

    authors: Silver DL,Montell DJ

    更新日期:2001-12-28 00:00:00

  • Displacement of sequence-specific transcription factors from mitotic chromatin.

    abstract::The general inhibition in transcriptional activity during mitosis abolishes the stress-inducible expression of the human hsp70 gene. Among the four transcription factors that bind to the human hsp70 promoter, the DNA-binding activities of three (C/EBP, GBP, and HSF1) were normal, while Sp1 showed reduced binding activ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(95)90231-7

    authors: Martínez-Balbás MA,Dey A,Rabindran SK,Ozato K,Wu C

    更新日期:1995-10-06 00:00:00

  • Heterozygous familial hypercholesterolemia: failure of normal allele to compensate for mutant allele at a regulated genetic locus.

    abstract::In normal human fibroblasts, the synthesis of a cell surface receptor for plasma low density lipoprotein (LDL) is regulated by a sensitive system of feedback suppression. The number of functional LDL receptors declines by more than 20 fold when cellular stores of esterified cholesterol are increased by incubation of c...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(76)90110-0

    authors: Goldstein JL,Sobhani MK,Faust JR,Brown MS

    更新日期:1976-10-01 00:00:00

  • From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II.

    abstract::RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ∼60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subd...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2013.07.033

    authors: Braberg H,Jin H,Moehle EA,Chan YA,Wang S,Shales M,Benschop JJ,Morris JH,Qiu C,Hu F,Tang LK,Fraser JS,Holstege FC,Hieter P,Guthrie C,Kaplan CD,Krogan NJ

    更新日期:2013-08-15 00:00:00

  • An Atomic Structure of the Human Spliceosome.

    abstract::Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C∗ complex) at an average resolution of 3.76 Å. The splicing factor Prp17...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2017.04.033

    authors: Zhang X,Yan C,Hang J,Finci LI,Lei J,Shi Y

    更新日期:2017-05-18 00:00:00

  • Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes.

    abstract::Pancreatic beta cell-surface expression of glucose transporter 2 (Glut-2) is essential for glucose-stimulated insulin secretion, thereby controlling blood glucose homeostasis in response to dietary intake. We show that the murine GlcNAcT-IVa glycosyltransferase is required for Glut-2 residency on the beta cell surface...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2005.09.041

    authors: Ohtsubo K,Takamatsu S,Minowa MT,Yoshida A,Takeuchi M,Marth JD

    更新日期:2005-12-29 00:00:00

  • A Friend in Need (of Nutrients) Is a….

    abstract::Endophytic fungi are found within the roots of healthy plants, but their function is poorly understood. In this issue, Hiruma et al. demonstrate that, under phosphate-limiting conditions, the endophytic fungus, Colletotrichum tofieldiae, provides growth-promoting and fitness benefits to Arabidopsis, but the plant must...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2016.03.036

    authors: Liberman LM,Benfey PN

    更新日期:2016-04-07 00:00:00

  • Breast cancer stem cells: eradication by differentiation therapy?

    abstract::During metastasis, migrating breast cancer stem cells undergo a loss of polarity leading to an epithelial-to-mesenchymal transition (EMT). Gupta et al. (2009) use this attribute of cancer stem cells to develop a high-throughput screen, which successfully identifies small molecules that specifically inhibit cancer stem...

    journal_title:Cell

    pub_type: 评论,杂志文章

    doi:10.1016/j.cell.2009.08.007

    authors: Beug H

    更新日期:2009-08-21 00:00:00

  • A notch-independent activity of suppressor of hairless is required for normal mechanoreceptor physiology.

    abstract::Suppressor of Hairless [Su(H)]/Lag-1/RBP-Jkappa/CBF1 is the only known transducing transcription factor for Notch receptor signaling. Here, we show that Su(H) has three distinct functions in the development of external mechanosensory organs in Drosophila: Notch-dependent transcriptional activation and a novel auto-rep...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/s0092-8674(00)00198-7

    authors: Barolo S,Walker RG,Polyanovsky AD,Freschi G,Keil T,Posakony JW

    更新日期:2000-12-08 00:00:00

  • Repressive Gene Regulation Synchronizes Development with Cellular Metabolism.

    abstract::Metabolic conditions affect the developmental tempo of animals. Developmental gene regulatory networks (GRNs) must therefore synchronize their dynamics with a variable timescale. We find that layered repression of genes couples GRN output with variable metabolism. When repressors of transcription or mRNA and protein s...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2019.06.023

    authors: Cassidy JJ,Bernasek SM,Bakker R,Giri R,Peláez N,Eder B,Bobrowska A,Bagheri N,Nunes Amaral LA,Carthew RW

    更新日期:2019-08-08 00:00:00

  • Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles.

    abstract::Loss of cell cycle control and acquisition of chromosomal rearrangements such as gene amplification often occur during tumor progression, suggesting that they may be correlated. We show here that the wild-type p53 allele is lost when fibroblasts from patients with the Li-Fraumeni syndrome (LFS) are passaged in vitro. ...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(92)90244-7

    authors: Yin Y,Tainsky MA,Bischoff FZ,Strong LC,Wahl GM

    更新日期:1992-09-18 00:00:00

  • Alternative splicing accounts for the four forms of myelin basic protein.

    abstract::We have isolated cDNA clones encoding the four different forms of mouse myelin basic protein (MBP) and have analyzed the structure of the MBP gene. The three larger forms of MBP differ from the smallest by the inclusion of either or both of two short amino acid sequences at positions 57 and 124 of the smallest protein...

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/0092-8674(85)90245-4

    authors: de Ferra F,Engh H,Hudson L,Kamholz J,Puckett C,Molineaux S,Lazzarini RA

    更新日期:1985-12-01 00:00:00

  • Organoid cultures derived from patients with advanced prostate cancer.

    abstract::The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells....

    journal_title:Cell

    pub_type: 杂志文章

    doi:10.1016/j.cell.2014.08.016

    authors: Gao D,Vela I,Sboner A,Iaquinta PJ,Karthaus WR,Gopalan A,Dowling C,Wanjala JN,Undvall EA,Arora VK,Wongvipat J,Kossai M,Ramazanoglu S,Barboza LP,Di W,Cao Z,Zhang QF,Sirota I,Ran L,MacDonald TY,Beltran H,Mosquera J

    更新日期:2014-09-25 00:00:00