Argonaute binding within 3'-untranslated regions poorly predicts gene repression.

Abstract:

:Despite two decades of study, the full scope of RNAi in mammalian cells has remained obscure. Here we combine: (i) Knockout of argonaute (AGO) variants; (ii) RNA sequencing analysis of gene expression changes and (iii) Enhanced Crosslinking Immunoprecipitation Sequencing (eCLIP-seq) using anti-AGO2 antibody to identify potential microRNA (miRNA) binding sites. We find that knocking out AGO1, AGO2 and AGO3 together are necessary to achieve full impact on steady state levels of mRNA. eCLIP-seq located AGO2 protein associations within 3'-untranslated regions. The standard mechanism of miRNA action would suggest that these associations should repress gene expression. Contrary to this expectation, associations between AGO and RNA are poorly correlated with gene repression in wild-type versus knockout cells. Many clusters are associated with increased steady state levels of mRNA in wild-type versus knock out cells, including the strongest cluster within the MYC 3'-UTR. Our results suggest that assumptions about miRNA action should be re-examined.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Chu Y,Kilikevicius A,Liu J,Johnson KC,Yokota S,Corey DR

doi

10.1093/nar/gkaa478

subject

Has Abstract

pub_date

2020-07-27 00:00:00

pages

7439-7453

issue

13

eissn

0305-1048

issn

1362-4962

pii

5851735

journal_volume

48

pub_type

杂志文章
  • DAP-like kinase interacts with the rat homolog of Schizosaccharomyces pombe CDC5 protein, a factor involved in pre-mRNA splicing and required for G2/M phase transition.

    abstract::DAP-like kinase (Dlk, also termed ZIP kinase) is a leucine zipper-containing serine/threonine-specific protein kinase with as yet unknown biological function(s). Interaction partners so far identified are either transcription factors or proteins that can support or counteract apoptosis. Thus, Dlk might be involved in ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/30.6.1408

    authors: Engemann H,Heinzel V,Page G,Preuss U,Scheidtmann KH

    更新日期:2002-03-15 00:00:00

  • The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog).

    abstract::The NHGRI-EBI GWAS Catalog has provided data from published genome-wide association studies since 2008. In 2015, the database was redesigned and relocated to EMBL-EBI. The new infrastructure includes a new graphical user interface (www.ebi.ac.uk/gwas/), ontology supported search functionality and an improved curation ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw1133

    authors: MacArthur J,Bowler E,Cerezo M,Gil L,Hall P,Hastings E,Junkins H,McMahon A,Milano A,Morales J,Pendlington ZM,Welter D,Burdett T,Hindorff L,Flicek P,Cunningham F,Parkinson H

    更新日期:2017-01-04 00:00:00

  • The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli.

    abstract::The CRISPR/Cas adaptive immune system provides resistance against phages and plasmids in Archaea and Bacteria. CRISPR loci integrate short DNA sequences from invading genetic elements that provide small RNA-mediated interference in subsequent exposure to matching nucleic acids. In Streptococcus thermophilus, it was pr...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr606

    authors: Sapranauskas R,Gasiunas G,Fremaux C,Barrangou R,Horvath P,Siksnys V

    更新日期:2011-11-01 00:00:00

  • 'Genome design' model and multicellular complexity: golden middle.

    abstract::Human tissue-specific genes were reported to be longer than housekeeping genes (both in coding and intronic parts). The competing neutralist and adaptationist models were proposed to explain this observation. Here I show that in human genome the longest are genes with the intermediate expression pattern. From the stan...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl773

    authors: Vinogradov AE

    更新日期:2006-01-01 00:00:00

  • Yeast two-hybrid junk sequences contain selected linear motifs.

    abstract::Yeast two-hybrid (Y2H) screenings result in identification of many out-of-frame (OOF) clones that code for short (2-100 amino acids) peptides with no sequence homology to known proteins. We hypothesize that these peptides can reveal common short linear motifs (SLiMs) responsible for their selection. We present a new p...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr600

    authors: Liu Y,Woods NT,Kim D,Sweet M,Monteiro AN,Karchin R

    更新日期:2011-10-01 00:00:00

  • Complete nucleotide sequence of alfalfa mosaic virus RNA 4.

    abstract::Alfalfa mosaic virus RNA 4, the subgenomic messenger for viral coat protein, was partially digested with RNase T1 or RNase A and the sequence of a number of fragments was deduced by in vitro labeling with polynucleotide kinase and application of RNA sequencing techniques. From overlapping fragments, the complete prima...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/8.10.2213

    authors: Brederode FT,Koper-Zwarthoff EC,Bol JF

    更新日期:1980-05-24 00:00:00

  • Identification of HDA15-PIF1 as a key repression module directing the transcriptional network of seed germination in the dark.

    abstract::Light is a major external factor in regulating seed germination. Photoreceptor phytochrome B (PHYB) plays a predominant role in promoting seed germination in the initial phase after imbibition, partially by repressing phytochrome-interacting factor1 (PIF1). However, the mechanism underlying the PHYB-PIF1-mediated tran...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx283

    authors: Gu D,Chen CY,Zhao M,Zhao L,Duan X,Duan J,Wu K,Liu X

    更新日期:2017-07-07 00:00:00

  • R-Coffee: a web server for accurately aligning noncoding RNA sequences.

    abstract::The R-Coffee web server produces highly accurate multiple alignments of noncoding RNA (ncRNA) sequences, taking into account predicted secondary structures. R-Coffee uses a novel algorithm recently incorporated in the T-Coffee package. R-Coffee works along the same lines as T-Coffee: it uses pairwise or multiple seque...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn278

    authors: Moretti S,Wilm A,Higgins DG,Xenarios I,Notredame C

    更新日期:2008-07-01 00:00:00

  • Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease- and ionizing radiation-induced DNA double-strand breaks.

    abstract::Non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSBs) is mediated by two protein complexes comprising Ku80/Ku70/DNA-PKcs/Artemis and XRCC4/LigaseIV/XLF. Loss of Ku or XRCC4/LigaseIV function compromises the rejoining of radiation-induced DSBs and leads to defective V(D)J recombination. In this study, we...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn094

    authors: Schulte-Uentrop L,El-Awady RA,Schliecker L,Willers H,Dahm-Daphi J

    更新日期:2008-05-01 00:00:00

  • Determinants of Nam8-dependent splicing of meiotic pre-mRNAs.

    abstract::Nam8, a component of yeast U1 snRNP, is optional for mitotic growth but required during meiosis, because Nam8 collaborates with Mer1 to promote splicing of essential meiotic mRNAs AMA1, MER2 and MER3. Here, we identify SPO22 and PCH2 as novel targets of Nam8-dependent meiotic splicing. Whereas SPO22 splicing is co-dep...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq1328

    authors: Qiu ZR,Schwer B,Shuman S

    更新日期:2011-04-01 00:00:00

  • Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome.

    abstract::While it has been long recognized that genes are not randomly positioned along the genome, the degree to which its 3D structure influences the arrangement of genes has remained elusive. In particular, several lines of evidence suggest that actively transcribed genes are spatially co-localized, forming transcription fa...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks1360

    authors: Ben-Elazar S,Yakhini Z,Yanai I

    更新日期:2013-02-01 00:00:00

  • Two step binding of HIV-1 reverse transcriptase to nucleic acid substrates.

    abstract::The interactions of HIV-1 reverse transcriptase (HIV-1 RT) with a synthetic 53/19-mer DNA substrate was investigated. For this template-primer HIV-1 RT displayed a Km value of 20 nM. The 53/19-mer competitively inhibited DNA synthesis performed on poly (rC).oligo(dG) with Ki value of 260 nM. This corresponded well to ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/21.17.3943

    authors: Kruhøffer M,Urbanke C,Grosse F

    更新日期:1993-08-25 00:00:00

  • Properties of a small transcribed poly A sequence in heterogeneous nuclear RNA of HeLa cells.

    abstract::A class of heterogeneous nuclear RNA (hnRNA) molecules contain an internal transcribed poly A sequence of close to 25 uninterrupted AMP residues. HnRNA molecules containing this sequence are separable from those containing the large 3' terminal poly A sequence on the basis of their differential affinity for oligo dT c...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/6.3.1097

    authors: Venkatesan S,Nakazato H,Kopp DW,Edmonds M

    更新日期:1979-03-01 00:00:00

  • Alkylation of template strand of coding region causes effective gene silencing.

    abstract::We recently developed a new type of pyrrole (Py)-imidazole (Im) polyamide-tetrahydrocyclopropabenzindolone (CBI) conjugate with an indole linker as a stable sequence-specific alkylating agent. In this study, we investigated the gene silencing activities of polyamides A, B and C, which selectively alkylate specific seq...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl005

    authors: Shinohara K,Sasaki S,Minoshima M,Bando T,Sugiyama H

    更新日期:2006-02-25 00:00:00

  • Sequence analysis and transcriptional regulation of the Escherichia coli grpE gene, encoding a heat shock protein.

    abstract::We have sequenced the Escherichia coli grpE gene and shown that it encodes a 197-amino acid residue protein of 21,668-Mr. The predicted N-terminal amino acid sequence, as well as the overall amino acid composition agree well with that of the purified protein. From Northern analysis, we have shown that transcription of...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/16.15.7545

    authors: Lipinska B,King J,Ang D,Georgopoulos C

    更新日期:1988-08-11 00:00:00

  • Protection of (dA.dT) cluster regions in the DNAase I cleavage of DNA by specific interaction with netropsin.

    abstract::The specific DNA binding ligand netropsin selectively blocks dA-dT base pairs in clusters containing two or more consecutive thymine residues at the dNAase I cleavage sites of DNA. Using CD and UV absorption measurements it is shown, that at various ratios of netropsin to nucleotide concentrations and even at satuatio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/8.13.2999

    authors: Zimmer C,Luck G,Nüske R

    更新日期:1980-07-11 00:00:00

  • Observations on template-specific conditions for DNA synthesis by avian myeloblastosis virus DNA polymerase.

    abstract::The effects of Mg++, Mn++, and KCl addition, individually and in combination, on the rate of DNA- and RNA-primed DNA synthesis by avian myeloblastosis virus DNA polymerase (reverse transcriptase) using a variety of natural and synthetic template-primer combinations were examined. Optimal divalent cation concentrations...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/3.6.1473

    authors: Marcus SL,Modak MJ

    更新日期:1976-06-01 00:00:00

  • AGMIAL: implementing an annotation strategy for prokaryote genomes as a distributed system.

    abstract::We have implemented a genome annotation system for prokaryotes called AGMIAL. Our approach embodies a number of key principles. First, expert manual annotators are seen as a critical component of the overall system; user interfaces were cyclically refined to satisfy their needs. Second, the overall process should be o...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl471

    authors: Bryson K,Loux V,Bossy R,Nicolas P,Chaillou S,van de Guchte M,Penaud S,Maguin E,Hoebeke M,Bessières P,Gibrat JF

    更新日期:2006-07-19 00:00:00

  • Combining structure probing data on RNA mutants with evolutionary information reveals RNA-binding interfaces.

    abstract::Systematic structure probing experiments (e.g. SHAPE) of RNA mutants such as the mutate-and-map (MaM) protocol give us a direct access into the genetic robustness of ncRNA structures. Comparative studies of homologous sequences provide a distinct, yet complementary, approach to analyze structural and functional proper...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw217

    authors: Reinharz V,Ponty Y,Waldispühl J

    更新日期:2016-06-20 00:00:00

  • The processing of repetitive extragenic palindromes: the structure of a repetitive extragenic palindrome bound to its associated nuclease.

    abstract::Extragenic sequences in genomes, such as microRNA and CRISPR, are vital players in the cell. Repetitive extragenic palindromic sequences (REPs) are a class of extragenic sequences, which form nucleotide stem-loop structures. REPs are found in many bacterial species at a high copy number and are important in regulation...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks741

    authors: Messing SA,Ton-Hoang B,Hickman AB,McCubbin AJ,Peaslee GF,Ghirlando R,Chandler M,Dyda F

    更新日期:2012-10-01 00:00:00

  • Predicting the functional impact of protein mutations: application to cancer genomics.

    abstract::As large-scale re-sequencing of genomes reveals many protein mutations, especially in human cancer tissues, prediction of their likely functional impact becomes important practical goal. Here, we introduce a new functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns. The ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr407

    authors: Reva B,Antipin Y,Sander C

    更新日期:2011-09-01 00:00:00

  • Telomeric repeats act as nucleosome-disfavouring sequences in vivo.

    abstract::Telomeric DNAs consist of tandem repeats of G-clusters such as TTAGGG and TG1-3, which are the human and yeast repeat sequences, respectively. In the yeast Saccharomyces cerevisiae, the telomeric repeats are non-nucleosomal, whereas in humans, they are organized in tightly packaged nucleosomes. However, previous in vi...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt1006

    authors: Ichikawa Y,Morohashi N,Nishimura Y,Kurumizaka H,Shimizu M

    更新日期:2014-02-01 00:00:00

  • The SRP9/14 subunit of the human signal recognition particle binds to a variety of Alu-like RNAs and with higher affinity than its mouse homolog.

    abstract::The heterodimeric subunit, SRP9/14, of the signal recognition particle (SRP) has previously been found to bind to scAlu and scB1 RNAs in vitro and to exist in large excess over SRP in anthropoid cells. Here we show that human and mouse SRP9/14 bind with high affinities to other Alu-like RNAs of different evolutionary ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.2.318

    authors: Bovia F,Wolff N,Ryser S,Strub K

    更新日期:1997-01-15 00:00:00

  • Primary and secondary structure of U2 snRNA.

    abstract::With the improved rapid sequencing techniques, the earlier sequence of U2 RNA of Novikoff hepatoma (Shibata et al, J. Biol. Chem. 250, 3909-3920, 1975) was reanalyzed and modified. The improved sequence of U2 RNA is 188 (or 189) nucleotides long and is in register with a characterized U2 RNA pseudogene (Denison et al,...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/9.21.5645

    authors: Reddy R,Henning D,Epstein P,Busch H

    更新日期:1981-11-11 00:00:00

  • A novel strategy for the negative selection in mouse embryonic stem cells operated with immunotoxin-mediated cell targeting.

    abstract::Immunotoxoin-mediated cell targeting (IMCT) is a technique for conditionally ablating specific cell types based on the cytotoxic activity of a recombinant immunotoxin anti-Tac (Fv)-PE40. To examine the feasibility of this technique for the negative selection in mouse embryonic stem (ES) cells, we investigated the resp...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/24.18.3653

    authors: Kobayashi K,Ohye T,Pastan I,Nagatsu T

    更新日期:1996-09-15 00:00:00

  • Biochemical analysis of the N-terminal domain of human RAD54B.

    abstract::The human RAD54B protein is a paralog of the RAD54 protein, which plays important roles in homologous recombination. RAD54B contains an N-terminal region outside the SWI2/SNF2 domain that shares less conservation with the corresponding region in RAD54. The biochemical roles of this region of RAD54B are not known, alth...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn516

    authors: Sarai N,Kagawa W,Fujikawa N,Saito K,Hikiba J,Tanaka K,Miyagawa K,Kurumizaka H,Yokoyama S

    更新日期:2008-10-01 00:00:00

  • Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1.

    abstract::We report the complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1, as 6633 base pairs of composition 79.5% G+C. This contains immediate early gene 3, encoding the IE175 protein, an important transcriptional activator of later virus genes. The IE175 coding region was identified...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.4.1727

    authors: McGeoch DJ,Dolan A,Donald S,Brauer DH

    更新日期:1986-02-25 00:00:00

  • An efficient string matching algorithm with k differences for nucleotide and amino acid sequences.

    abstract::There are a few algorithms designed to solve the problem of the optimal alignment of one sequence, the pattern, of length m, with another, longer sequence the text, of length n. These algorithms allow mismatches, deletions and insertions. Algorithms to date run in O(mn) time. Let us define an integer, k, which is the ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.1.31

    authors: Landau GM,Vishkin U,Nussinov R

    更新日期:1986-01-10 00:00:00

  • Global translation inhibition yields condition-dependent de-repression of ribosome biogenesis mRNAs.

    abstract::Ribosome biogenesis (RiBi) is an extremely energy intensive process that is critical for gene expression. It is thus highly regulated, including through the tightly coordinated expression of over 200 RiBi genes by positive and negative transcriptional regulators. We investigated RiBi regulation as cells initiated meio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz231

    authors: Cheng Z,Brar GA

    更新日期:2019-06-04 00:00:00

  • In situ hybridization with fluoresceinated DNA.

    abstract::We have used fluorescein-11-dUTP in a nick-translation format to produce fluoresceinated human nucleic acid probes. After in situ hybridization of fluoresceinated DNAs to human metaphase chromosomes, the detection sensitivity was found to be 50-100 kb. The feasibility and the increase in detection sensitivity of micro...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.12.3237

    authors: Wiegant J,Ried T,Nederlof PM,van der Ploeg M,Tanke HJ,Raap AK

    更新日期:1991-06-25 00:00:00