SIDT2 mediates gymnosis, the uptake of naked single-stranded oligonucleotides into living cells.

Abstract:

:Single-stranded oligonucleotides (ssOligos) are efficiently taken up by living cells without the use of transfection reagents. This phenomenon called 'gymnosis' enables the sequence-specific silencing of target genes in various types of cells. Several antisense ssOligos are used for the treatment of human diseases. However, the molecular mechanism underlying the uptake of naked ssOligos into cells remains to be elucidated. Here, we show that systemic RNA interference deficient-1 (SID-1) transmembrane family 2 (SIDT2), a mammalian ortholog of the Caenorhabditis elegans double-stranded RNA channel SID-1, mediates gymnosis. We show that the uptake of naked ssOligos into cells is significantly downregulated by knockdown of SIDT2. Furthermore, knockdown of SIDT2 inhibited the effect of antisense RNA mediated by gymnosis. Overexpression of SIDT2 enhanced the uptake of naked ssOligos into cells, while a single amino acid mutation in SIDT2 abolished this effect. Our findings highlight the mechanism of extra- and intracellular RNA transport and may contribute to the further development of nucleic acid-based therapies.

journal_name

RNA Biol

journal_title

RNA biology

authors

Takahashi M,Contu VR,Kabuta C,Hase K,Fujiwara Y,Wada K,Kabuta T

doi

10.1080/15476286.2017.1302641

subject

Has Abstract

pub_date

2017-11-02 00:00:00

pages

1534-1543

issue

11

eissn

1547-6286

issn

1555-8584

journal_volume

14

pub_type

杂志文章
  • Novel, abundant Drosha isoforms are deficient in miRNA processing in cancer cells.

    abstract::MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licenced by the ribonuclease (RNase) III enzyme Drosha, the regulatio...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1813439

    authors: Dai L,Hallmark L,Bofill De Ros X,Crouch H,Chen S,Shi T,Yang A,Lian C,Zhao Y,Tran B,Gu S

    更新日期:2020-11-01 00:00:00

  • A new fungus-mediated RNAi method established and used to study the fatty acid and retinol binding protein function of the plant-parasitic nematode Aphelenchoides besseyi.

    abstract::RNA interference (RNAi) is a powerful tool for gene functional analysis of plant-parasitic nematodes (PPNs). RNAi involving soaking in a dsRNA solution and in planta methods is commonly applied in the study of gene function in PPNs. However, certain problems restrict the application of these methods. Therefore, more c...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1852779

    authors: Ding S,Wang D,Xu C,Yang S,Cheng X,Peng X,Chen C,Xie H

    更新日期:2020-12-14 00:00:00

  • RBM4-MEF2C network constitutes a feed-forward circuit that facilitates the differentiation of brown adipocytes.

    abstract::Myocyte enhancer factor 2c (MEF2C) is the MADS-box type transcription factor involved in the differentiation of cardiac and skeletal muscle and synaptic formation. Alternatively spliced transcripts of the MEF2C gene were proven to encode isoforms which exert distinct functions in transcriptional regulation. During the...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2015.1017213

    authors: Lin JC

    更新日期:2015-01-01 00:00:00

  • IF2 and unique features of initiator tRNAfMet help establish the translational reading frame.

    abstract::Translation begins at AUG, GUG, or UUG codons in bacteria. Start codon recognition occurs in the P site, which may help explain this first-position degeneracy. However, the molecular basis of start codon specificity remains unclear. In this study, we measured the codon dependence of 30S•mRNA•tRNAfMet and 30S•mRNA•tRNA...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2017.1379636

    authors: Roy B,Liu Q,Shoji S,Fredrick K

    更新日期:2018-01-01 00:00:00

  • RNA-protein coevolution study of Gemin5 uncovers the role of the PXSS motif of RBS1 domain for RNA binding.

    abstract::Regulation of protein synthesis is an essential step of gene expression. This process is under the control of cis-acting RNA elements and trans-acting factors. Gemin5 is a multifunctional RNA-binding protein organized in distinct domains. The protein bears a non-canonical RNA-binding site, designated RBS1, at the C-te...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1762054

    authors: Francisco-Velilla R,Embarc-Buh A,Rangel-Guerrero S,Basu S,Kundu S,Martinez-Salas E

    更新日期:2020-09-01 00:00:00

  • Pentatricopeptide repeats: modular blocks for building RNA-binding proteins.

    abstract::Pentatricopeptide repeat (PPR) proteins control diverse aspects of RNA metabolism across the eukaryotic domain. Recent computational and structural studies have provided new insights into how they recognize RNA, and show that the recognition is sequence-specific and modular. The modular code for RNA-binding by PPR pro...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.24769

    authors: Filipovska A,Rackham O

    更新日期:2013-01-01 00:00:00

  • High-affinity interaction of hnRNP A1 with conserved RNA structural elements is required for translation and replication of enterovirus 71.

    abstract::Human Enterovirus 71 (EV71) is an emerging pathogen of infectious disease and a serious threat to public health. Currently, there are no antivirals or vaccines to slow down or prevent EV71 infections, thus underscoring the urgency to better understand mechanisms of host-enterovirus interactions. EV71 uses a type I int...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.25107

    authors: Levengood JD,Tolbert M,Li ML,Tolbert BS

    更新日期:2013-07-01 00:00:00

  • Gene expression as a circular process: cross-talk between transcription and mRNA degradation in eukaryotes; International University of Andalusia (UNIA) Baeza, Spain.

    abstract::Studies on the regulation of gene expression in eukaryotes in the past 20 years have consistently revealed increasing levels of complexity. Thirty years ago it seemed that we had understood the basic principles of gene regulation in eukaryotes. It was thought that regulation of transcription was the first and most imp...

    journal_title:RNA biology

    pub_type:

    doi:10.4161/rna.28037

    authors: Collart MA,Reese JC

    更新日期:2014-01-01 00:00:00

  • Linking the association between circRNAs and Alzheimer's disease progression by multi-tissue circular RNA characterization.

    abstract::Alzheimer's disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1783487

    authors: Lo I,Hill J,Vilhjálmsson BJ,Kjems J

    更新日期:2020-12-01 00:00:00

  • The importance of helix P1 stability for structural pre-organization and ligand binding affinity of the adenine riboswitch aptamer domain.

    abstract::We report here an in-depth characterization of the aptamer domain of the transcriptional adenine-sensing riboswitch (pbuE) by NMR and fluorescence spectroscopy. By NMR studies, the structure of two aptamer sequences with different lengths of the helix P1, the central element involved in riboswitch conformational switc...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.29439

    authors: Nozinovic S,Reining A,Kim YB,Noeske J,Schlepckow K,Wöhnert J,Schwalbe H

    更新日期:2014-01-01 00:00:00

  • Toward a crystal-clear view of the viral RNA sensing and response by RIG-I-like receptors.

    abstract::The RIG-I-like receptors (RLRs)--RIG-I, MDA5, and LGP2--detect intracellular pathogenic RNA and elicit an antiviral immune response during viral infection. The protein architecture of the RLR family consists of multiple functional domains, including N-terminal Caspase Activation and Recruitment Domains (CARDs) for sig...

    journal_title:RNA biology

    pub_type: 杂志文章,评审

    doi:10.4161/rna.27717

    authors: Luo D

    更新日期:2014-01-01 00:00:00

  • miR-206 knockout shows it is critical for myogenesis and directly regulates newly identified target mRNAs.

    abstract::The muscle specific miRNA, miR-206, is important for the process of myogenesis; however, studying the function of miR-206 in muscle development and differentiation still proves challenging because the complement of mRNA targets it regulates remains undefined. In addition, miR-206 shares close sequence similarity to mi...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1737443

    authors: Salant GM,Tat KL,Goodrich JA,Kugel JF

    更新日期:2020-07-01 00:00:00

  • Conserved microRNA miR-8 blocks activation of the Toll pathway by upregulating Serpin 27 transcripts.

    abstract::microRNAs (miRNAs) play significant regulatory roles in gene expression at the post-transcriptional level. This includes modulating processes such as development, immunity, cancer, and host-pathogen interactions. It was recently shown that the phylogenetically deeply conserved miRNA, miR-8, plays a role in maintaining...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.25481

    authors: Etebari K,Asgari S

    更新日期:2013-08-01 00:00:00

  • Evolution of the miR199-214 cluster and vertebrate skeletal development.

    abstract::MicroRNA (miRs) are short non-coding RNAs that fine-tune the regulation of gene expression to coordinate a wide range of biological processes. MicroRNAs are transcribed from miR genes and primary miR transcripts are processed to approximately 22 nucleotide single strand mature forms that function as repressors of tran...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.28141

    authors: Desvignes T,Contreras A,Postlethwait JH

    更新日期:2014-01-01 00:00:00

  • Long non-coding RNA TUG1 and its molecular mechanisms in polycystic ovary syndrome.

    abstract::Polycystic ovary syndrome (PCOS) causes anovulatory infertility in women of reproductive age, but etiopathogenesis of PCOS remains undetermined. Taurine up-regulated 1 (TUG1), an evolutionarily conserved long non-coding RNA, performs various biological functions; however, the role of TUG1 in PCOS remains unclear. Here...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1783850

    authors: Li Y,Zhang J,Liu YD,Zhou XY,Chen X,Zhe J,Zhang QY,Zhang XF,Chen YX,Wang Z,Chen SL

    更新日期:2020-12-01 00:00:00

  • Crystallographic and mutational studies of seryl-tRNA synthetase from the archaeon Pyrococcus horikoshii.

    abstract::Seryl-tRNA synthetase (SerRS) catalyzes the ligation of serine to the 3'-end of serine tRNA (tRNA(Ser)), which is typical of the type-2 tRNAs characterized by a long extra arm. The SerRSs are divided into two types, the archaeal/eukaryal and bacterial types. In this study, we solved the crystal structures of the SerRS...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.5.3.6876

    authors: Itoh Y,Sekine S,Kuroishi C,Terada T,Shirouzu M,Kuramitsu S,Yokoyama S

    更新日期:2008-07-01 00:00:00

  • Effect of mutations on the p53 IRES RNA structure: implications for de-regulation of the synthesis of p53 isoforms.

    abstract::Earlier we have demonstrated the presence of internal ribosome entry site (IRES) within tumor suppressor p53 mRNA. Here we have mapped the putative secondary structure of p53- IRES RNA using information from chemical probing and nuclease mapping experiments. Additionally, the secondary structure of the IRES element of...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.8.1.14260

    authors: Grover R,Sharathchandra A,Ponnuswamy A,Khan D,Das S

    更新日期:2011-01-01 00:00:00

  • Opposing roles of C/EBPα and eEF1A1 in Sp1-regulated miR-122 transcription.

    abstract::We previously showed that miR-122 was frequently downregulated in hepatocellular carcinoma (HCC) and C/EBPα transactivated miR-122 expression. In this study, we found that Sp1 bound to the miR-122 promoter at two different sites. Interestingly, either inhibition or overexpression of Sp1 could decrease the miR-122 prom...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2019.1673656

    authors: Zeng C,Sang Y,Wang FY,Zhuang SM

    更新日期:2020-02-01 00:00:00

  • The chemistries and consequences of DNA and RNA methylation and demethylation.

    abstract::Chemical modification of nucleobases plays an important role for the control of gene expression on different levels. That includes the modulation of translation by modified tRNA-bases or silencing and reactivation of genes by methylation and demethylation of cytosine in promoter regions. Especially dynamic methylation...

    journal_title:RNA biology

    pub_type: 杂志文章,评审

    doi:10.1080/15476286.2017.1318241

    authors: Traube FR,Carell T

    更新日期:2017-09-02 00:00:00

  • The 70S ribosome modulates the ATPase activity of Escherichia coli YchF.

    abstract::YchF is one of two universally conserved GTPases with unknown cellular function. As a first step toward elucidating YchF's cellular role, we performed a detailed biochemical characterization of the protein from Escherichia coli. Our data from fluorescence titrations not only confirmed the surprising finding that YchFE...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.22131

    authors: Becker M,Gzyl KE,Altamirano AM,Vuong A,Urban K,Wieden HJ

    更新日期:2012-10-01 00:00:00

  • Casting a long shadow in the classroom: an educator's perspective of the contributions of Carl Woese.

    abstract::"What does one do when the giants pass away?" remarked a very famous microbiologist to me, soon after the death of Carl Woese in late 2012. I teach microbiology and introductory cell and molecular biology at a small undergraduate institution; Woese's example and contributions have long been part of every class I teach...

    journal_title:RNA biology

    pub_type: 杂志文章,评审

    doi:10.4161/rna.28002

    authors: Martin M

    更新日期:2014-01-01 00:00:00

  • The anti-cancer drug 5-fluorouracil affects cell cycle regulators and potential regulatory long non-coding RNAs in yeast.

    abstract::5-fluorouracil (5-FU) was isolated as an inhibitor of thymidylate synthase, which is important for DNA synthesis. The drug was later found to also affect the conserved 3'-5' exoribonuclease EXOSC10/Rrp6, a catalytic subunit of the RNA exosome that degrades and processes protein-coding and non-coding transcripts. Work ...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2019.1581596

    authors: Xie B,Becker E,Stuparevic I,Wery M,Szachnowski U,Morillon A,Primig M

    更新日期:2019-06-01 00:00:00

  • Chaperna: linking the ancient RNA and protein worlds.

    abstract::As a mental framework for the transition of self-replicating biological forms, the RNA world concept stipulates a dual function of RNAs as genetic substance and catalyst. The chaperoning function is found intrinsic to ribozymes involved in protein synthesis and tRNA maturation, enriching the primordial RNA world with ...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1801199

    authors: Son A,Horowitz S,Seong BL

    更新日期:2021-01-01 00:00:00

  • Constraint and opportunity in genome innovation.

    abstract::The development of rigorous molecular taxonomy pioneered by Carl Woese has freed evolution science to explore numerous cellular activities that lead to genome change in evolution. These activities include symbiogenesis, inter- and intracellular horizontal DNA transfer, incorporation of DNA from infectious agents, and ...

    journal_title:RNA biology

    pub_type: 杂志文章,评审

    doi:10.4161/rna.27506

    authors: Shapiro JA

    更新日期:2014-01-01 00:00:00

  • Natural variation of the cardiac transcriptome in humans.

    abstract::We investigated the gene-expression variation among humans by analysing previously published mRNA-seq and ribosome footprint profiling of heart left-ventricles from healthy donors. We ranked the genes according to their coefficient of variation values and found that the top 5% most variable genes had special features ...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2020.1857508

    authors: Domitrovic T,Moreira MH,Carneiro RL,Ribeiro-Alves M,Palhano FL

    更新日期:2020-12-11 00:00:00

  • Long noncoding RNA in genome regulation: prospects and mechanisms.

    abstract::Long noncoding RNAs (lncRNAs) are pervasively transcribed and critical regulators of the epigenome[1, 2]. These long, polyadenylated RNAs do not code for proteins, but function directly as RNAs, recruiting chromatin modifiers to mediate transcriptional changes in processes ranging from X-inactivation (XIST) to imprint...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.7.5.13216

    authors: Hung T,Chang HY

    更新日期:2010-09-01 00:00:00

  • Reconstitution of chromatoid body-like particles in cultured cells: a novel approach to elucidate the mechanism of assembly and function of the chromatoid body.

    abstract::The chromatoid body is a large perinuclear ribonucleoprotein particle of germ cells. The chromatoid body is also present in stem cells from planarians. This particle shares markers specific to protein aggresomes and P-bodies, and concentrate several RNA pathways. The assembly mechanism of chromatoid bodies is unknown,...

    journal_title:RNA biology

    pub_type: 杂志文章,评审

    doi:10.4161/rna.6.2.8049

    authors: Roucou X

    更新日期:2009-04-01 00:00:00

  • Decoding the noncoding: prospective of lncRNA-mediated innate immune regulation.

    abstract::The innate immune system is the first line of defense against microbial pathogens, but tight regulation of gene expression is necessary to prevent the detrimental effects of unrestrained activation. Although the functions of most long noncoding RNAs (lncRNAs; >200 nucleotides) are unknown, many have been shown to regu...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.29937

    authors: Li Z,Rana TM

    更新日期:2014-01-01 00:00:00

  • Regulatory roles of vertebrate Nocturnin: insights and remaining mysteries.

    abstract::Post-transcriptional control of messenger RNA (mRNA) is an important layer of gene regulation that modulates mRNA decay, translation, and localization. Eukaryotic mRNA decay begins with the catalytic removal of the 3' poly-adenosine tail by deadenylase enzymes. Multiple deadenylases have been identified in vertebrates...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.1080/15476286.2018.1526541

    authors: Hughes KL,Abshire ET,Goldstrohm AC

    更新日期:2018-01-01 00:00:00

  • Variations on the tmRNA gene.

    abstract::tmRNA employs both tRNA-like and mRNA-like properties as it rescues stalled bacterial ribosomes, while targeting the defective mRNA and incomplete nascent protein for degradation. We describe variation of the tmRNA gene (ssrA) and how it informs tmRNA structure and function. Endosymbiont tmRNAs tend to lose secondary ...

    journal_title:RNA biology

    pub_type: 杂志文章

    doi:10.4161/rna.6.4.9172

    authors: Mao C,Bhardwaj K,Sharkady SM,Fish RI,Driscoll T,Wower J,Zwieb C,Sobral BW,Williams KP

    更新日期:2009-09-01 00:00:00