Abstract:
:Although the involvement of Ser/Arg-rich (SR) proteins in RNA metabolism is well documented, their role in vertebrate development remains elusive. We, therefore, elected to take advantage of the zebrafish model organism to study the SR genes' functions using the splicing morpholino (sMO) microinjection and the programmable site-specific nucleases. Consistent with previous research, we revealed discrepancies between the mutant and morphant phenotypes and we show that these inconsistencies may result from a large number of unsuspected inadvertent morpholino RNA targets. While microinjection of MOs directed against srsf5a (sMOsrsf5a) led to developmental defects, the corresponding homozygous mutants did not display any phenotypic traits. Furthermore, microinjection of sMOsrsf5a into srsf5a-/- led to the previously observed morphant phenotype. Similar findings were observed for other SR genes. sMOsrsf5a alternative target genes were identified using deep mRNA sequencing. We uncovered that only 11 consecutive bases complementary to sMOsrsf5a are sufficient for binding and subsequent blocking of splice sites. In addition, we observed that sMOsrsf5a secondary targets can be reduced by increasing embryos growth temperature after microinjection. Our data contribute to the debate about MO specificity, efficacy and the number of unknown targeted sequences.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Joris M,Schloesser M,Baurain D,Hanikenne M,Muller M,Motte Pdoi
10.1093/nar/gkx638subject
Has Abstractpub_date
2017-09-19 00:00:00pages
9547-9557issue
16eissn
0305-1048issn
1362-4962pii
3984534journal_volume
45pub_type
杂志文章abstract::MicroRNAs (miRNAs) are approximately 22 nucleotide (nt) long and play important roles in post-transcriptional regulation in both plants and animals. In animals, precursor (pre-) miRNAs are ∼70 nt hairpins produced by Drosha cleavage of long primary (pri-) miRNAs in the nucleus. Exportin-5 (XPO5) transports pre-miRNAs ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky306
更新日期:2018-06-20 00:00:00
abstract::Using synthetic oligodeoxyribonucleotides to prime the transcription of interferon mRNA and cDNA, we recently determined the mRNA sequence coding for the 47 amino-terminal amino acids of mature human fibroblast interferon (1). From this sequence, we have now synthesised an oligodeoxyribonucleotide that is homologous w...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/8.13.2885
更新日期:1980-07-11 00:00:00
abstract::MicroRNAs (miRNAs) are short, non-protein coding RNAs that direct the widespread phenomenon of post-transcriptional regulation of metazoan genes. The mature approximately 22-nt long RNA molecules are processed from genome-encoded stem-loop structured precursor genes. Hundreds of such genes have been experimentally val...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn707
更新日期:2009-01-01 00:00:00
abstract::Adenine, thymine and cytosine PNA monomers have been prepared using 3-amino-1,2-propanediol as a starting material. The benzoyl group was used to protect the exocyclic amines of the heterocyclic bases of A and C PNA monomers and the backbone primary amine was protected with the monomethoxytrityl group. The thymine and...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.17.3357
更新日期:1996-09-01 00:00:00
abstract::Mutations help us to understand the molecular origins of diseases. Researchers, therefore, both publish and seek disease-relevant mutations in public databases and in scientific literature, e.g. Medline. The retrieval tends to be time-consuming and incomplete. Automated screening of the literature is more efficient. W...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh162
更新日期:2004-01-02 00:00:00
abstract::Homologous recombination (HR) is a highly accurate mechanism of DNA repair that can be exploited for homology-directed gene targeting. Since in most cell types HR occurs very infrequently (approximately 10(-6) to 10(-8)), its practical application has been largely restricted to specific experimental systems that allow...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp643
更新日期:2009-09-01 00:00:00
abstract::The Escherichia coli RuvC protein is an endonuclease that resolves Holliday junctions. In vitro, the protein shows efficient structure-specific binding of Holliday junctions, yet the rate of junction resolution is remarkably low. We have mapped the sites of cleavage on a synthetic junction through which a crossover ca...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.13.2490
更新日期:1994-07-11 00:00:00
abstract::RNA structural complexity and flexibility present a challenge for computational modeling efforts. Experimental information and bioinformatics data can be used as restraints to improve the accuracy of RNA tertiary structure prediction. Regarding utilization of restraints, the fundamental questions are: (i) What is the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz427
更新日期:2019-06-20 00:00:00
abstract::Two models have been proposed for triggering release of the lagging strand polymerase at the replication fork, enabling cycling to the primer for the next Okazaki fragment--either collision with the 5'-end of the preceding fragment (collision model) or synthesis of a new primer by primase (signaling model). Specific p...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1098
更新日期:2014-02-01 00:00:00
abstract::Furvina®, also denominated G1 (MW 297), is a synthetic nitrovinylfuran [2-bromo-5-(2-bromo-2-nitrovinyl)-furan] antibiotic with a broad antimicrobial spectrum. An ointment (Dermofural®) containing G1 as the only active principle is currently marketed in Cuba and successfully used to treat dermatological infections. He...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks822
更新日期:2012-11-01 00:00:00
abstract::We describe a dedicated RNA motif search program and web server to identify RNA riboswitches. The Riboswitch finder analyses a given sequence using the web interface, checks specific sequence elements and secondary structure, calculates and displays the energy folding of the RNA structure and runs a number of tests in...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh352
更新日期:2004-07-01 00:00:00
abstract::Poly(pyrimidine) . poly(purine) tracts have been discovered in the 5'-flanking regions of many eucaryotic genes. They may be involved in the regulation of expression since they can be mapped to the nuclease-sensitive sites of active chromatin. We have found that poly(pyrimidine) . poly(purine) DNAs which contain 5-met...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.16.6603
更新日期:1984-08-24 00:00:00
abstract::Type I toxin-antitoxin (TA) systems have been identified in a wide range of bacterial genomes. Here, we report the characterization of a new type I TA system present on the chromosome of the major human gastric pathogen, Helicobacter pylori. We show that the aapA1 gene encodes a 30 amino acid peptide whose artificial ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw1343
更新日期:2017-05-05 00:00:00
abstract::One of the most intensively studied chromatin binding factors is HP1α. HP1α is associated with silenced, heterochromatic regions of the genome and binds to H3K9me3. While H3K9me3 is necessary for HP1α recruitment to heterochromatin, it is becoming apparent that it is not sufficient suggesting that additional factors a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky632
更新日期:2018-10-12 00:00:00
abstract::Large-scale automatic annotation of protein sequences remains challenging in postgenomics era. E1DS is designed for annotating enzyme sequences based on a repository of 1D signatures. The employed sequence signatures are derived using a novel pattern mining approach that discovers long motifs consisted of several sequ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn324
更新日期:2008-07-01 00:00:00
abstract::Base excision repair (BER), which is initiated by DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. The NTHL1 glycosylase, which excises DNA base damage caused by reactive oxygen species, is thought to be a tumor suppressor. However, in addition to NTHL1 loss-of-function...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky162
更新日期:2018-05-18 00:00:00
abstract::Two triple helix structures (15-mers containing only T.A-T triplets or containing mixed T.A-T and C.G-C triplets) have been studied by uranyl mediated DNA photocleavage to probe the accessibility of the phosphates of the DNA backbone. Whereas the phosphates of the pyrimidine strand are at least as accessible as in dou...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.11.2735
更新日期:1992-06-11 00:00:00
abstract::The DNA sequence of the spacer (plus flanking) regions separating the 16S rRNA and 23S rRNA genes of two presumptive rDNA operons of the archaebacterium Methanococcus vannielii was determined. The spacers are 156 and 242 base pairs in size and they share a sequence homology of 49 base pairs following the 3' terminus o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.21.7537
更新日期:1983-11-11 00:00:00
abstract::Nucleotide sequences of three cloned restriction fragments of Tetrahymena mtDNA which showed hybridization with mitochondrial tRNA have been determined. EcoRI fragment 5 (4.1 kbp) contains the tRNAphe gene sequence with anticodon GAA; Hind III fragment 6 (2.0 kbp) the tRNAhis with anticodon GTG; and EcoRI fragment 7 (...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.9.3273
更新日期:1985-05-10 00:00:00
abstract::In bacteria, promoter identification by RNA polymerase is mediated by a dissociable σ factor. The housekeeping σ(70) factor of Escherichia coli recognizes two well characterized DNA sequence elements, known as the '-10' and '-35' hexamers. These elements are separated by 'spacer' DNA, the sequence of which is generall...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr080
更新日期:2011-07-01 00:00:00
abstract::We describe a new exonuclease-based method for joining and/or constructing two or more DNA molecules. DNA fragments containing ends complementary to those of a vector or another independent molecules were generated by the polymerase chain reaction. The 3' ends of these molecules as well as the vector DNA were then rec...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.8.1889
更新日期:1993-04-25 00:00:00
abstract::The cDNA of human DNA polymerase delta was cloned. The cDNA had a length of 3.5 kb and encoded a protein of 1107 amino acid residues with a calculated molecular mass of 124 kDa. Northern blot analysis showed that the cDNA hybridized to a mRNA of 3.4 kb. Monoclonal and polyclonal antibodies to the C-terminal 20 residue...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.4.735
更新日期:1992-02-25 00:00:00
abstract::We present a www server for AUGUSTUS, a novel software program for ab initio gene prediction in eukaryotic genomic sequences. Our method is based on a generalized Hidden Markov Model with a new method for modeling the intron length distribution. This method allows approximation of the true intron length distribution m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh379
更新日期:2004-07-01 00:00:00
abstract::Many microRNAs (miRNAs) are co-regulated during the same physiological process but the underlying cellular logic is often little understood. The conserved, immunomodulatory miRNAs miR-146 and miR-155, for instance, are co-induced in many cell types in response to microbial lipopolysaccharide (LPS) to feedback-repress ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1030
更新日期:2013-01-07 00:00:00
abstract::The use of bacterial artificial chromosomes (BACs) provides a consistent and high targeting efficiency of homologous recombination in embryonic stem (ES) cells, facilitated by long stretches of sequence homology. Here, we introduce a BAC targeting method which employs restriction fragment length polymorphisms (RFLPs) ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr550
更新日期:2011-10-01 00:00:00
abstract::We present NetCore, a novel network propagation approach based on node coreness, for phenotype-genotype associations and module identification. NetCore addresses the node degree bias in PPI networks by using node coreness in the random walk with restart procedure, and achieves improved re-ranking of genes after propag...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa639
更新日期:2020-09-25 00:00:00
abstract::Cultured mammalian cells transduced with the Escherichia coli gene, Ecogpt, synthesize the bacterial enzyme xanthine-guanine phosphoribosyl transferase (XGPT) (1). This paper describes a method for measuring XGPT activity in crude cell extracts by following the conversion of 14C-xanthine (X) to 14C-xanthine monophosph...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.8.2921
更新日期:1985-04-25 00:00:00
abstract::Over the past 10 years, fluorescent end-labeling of DNA fragments has evolved into the preferred method of DNA detection for a wide variety of applications, including DNA sequencing and PCR fragment analysis. One of the advantages inherent in fluorescent detection methods is the ability to perform multi-color analyses...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.11.2797
更新日期:1998-06-01 00:00:00
abstract::Effective transcript profiling in animal systems requires isolation of homogenous tissue or cells followed by faithful mRNA amplification. Linear amplification based on cDNA synthesis and in vitro transcription is reported to maintain representation of mRNA levels, however, quantitative data demonstrating this as well...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.5.e29
更新日期:2001-03-01 00:00:00
abstract::Chromatin immunoprecipitation (ChIP) has ushered in a new era of scientific discovery by allowing new insights into DNA-protein interactions. ChIP is used to quantify enriched genomic regions using qPCR, and more recently is combined with next generation sequencing (ChIP-seq) to obtain a genome wide profile of protein...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky813
更新日期:2019-01-08 00:00:00