A Mouse Cytoplasmic Exoribonuclease (mXRN1p) with Preference for G4 Tetraplex Substrates

Bashkirov, Vladimir I.; Scherthan, Harry; Solinger, Jachen A.; Buerstedde, Jean Marie; Heyer, Wolf Dietrich

doi:10.1083/jcb.136.4.761

Cited by 326 publications

(252 citation statements)

References 75 publications

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“…GWB are named from the marker protein GW182, which contains multiple glycine (G) and tryptophan (W) repeats and a classic RNA binding domain at the carboxyl terminus (Eystathioy et al, 2002a). The mRNA decay factors/complexes found in GWB include the deadenylase Ccr4, the decapping complex Dcp1a/1b/Dcp2, the LSm1-7 complex, Ge-1 (also known as Hedls), rck/p54, and exonuclease Xrn1 (Bashkirov et al, 1997;van Dijk et al, 2002;Ingelfinger et al, 2002;Lykke-Andersen, 2002;Eystathioy et al, 2003;Cougot et al, 2004;Andrei et al, 2005;Yu et al, 2005;Fenger-Gron et al, 2005). GWB are physically juxtaposed to and transiently interact with stress granules (SG).…”

Section: Introductionmentioning

confidence: 99%

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

Lian¹,

Fritzler

Katz³

et al. 2007

MBoC

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Gene silencing using small interfering RNA (siRNA) is a valuable laboratory tool and a promising approach to therapeutics for a variety of human diseases. Recently, RNA interference (RNAi) has been linked to cytoplasmic GW bodies (GWB). However, the correlation between RNAi and the formation of GWB, also known as mammalian processing bodies, remains unclear. In this report, we show that transfection of functional siRNA induced larger and greater numbers of GWB. This siRNA-induced increase of GWB depended on the endogenous expression of the target mRNA. Knockdown of GW182 or Ago2 demonstrated that the siRNA-induced increase of GWB required these two proteins and correlated with RNAi. Furthermore, knockdown of rck/p54 or LSm1 did not prevent the reassembly of GWB that were induced by and correlated with siRNA-mediated RNA silencing. We propose that RNAi is a key regulatory mechanism for the assembly of GWB, and in some cases, GWB may serve as markers for RNAi in mammalian cells. INTRODUCTIONGW bodies (GWB), also known as mammalian processing bodies (P bodies), are cytoplasmic foci that contain multiple decay factors and that are involved in the 5Ј33Ј mRNA degradation pathway. GWB are named from the marker protein GW182, which contains multiple glycine (G) and tryptophan (W) repeats and a classic RNA binding domain at the carboxyl terminus (Eystathioy et al., 2002a). The mRNA decay factors/complexes found in GWB include the deadenylase Ccr4, the decapping complex Dcp1a/1b/Dcp2, the LSm1-7 complex, Ge-1 (also known as Hedls), rck/p54, and exonuclease Xrn1 (Bashkirov et al., 1997;van Dijk et al., 2002;Ingelfinger et al., 2002;Lykke-Andersen, 2002;Eystathioy et al., 2003;Cougot et al., 2004;Andrei et al., 2005;Yu et al., 2005;Fenger-Gron et al., 2005). GWB are physically juxtaposed to and transiently interact with stress granules (SG). SG process cytoplasmic aggregates of stalled translational preinitiation complexes that accumulate during stress responses and that share certain components with GWB (Kedersha et al., 2005).In addition to mRNA decay, a crucial role of GWB and their components in RNA interference (RNAi) was recently uncovered (Anderson and Kedersha, 2006;Eulalio et al., 2007a;Jakymiw et al., 2007). RNAi is a posttranscriptional gene silencing mechanism that uses specific doublestranded RNA to silence genes in a sequence-specific manner Mello and Conte, 2004). In brief, the double-stranded RNA is processed by Dicer into small interfering RNA (siRNA) or microRNA (miRNA). The 21-to 26-nucleotide siRNA and miRNA are then incorporated in the effector complex, RNA-induced silencing complex (RISC), which either cleaves or inhibits translation of the target mRNA. In 2005, two key components of RISC, Argonaute2 (Ago2) and siRNA/miRNA, were found to be enriched in GWB (Sen and Blau, 2005;Pillai et al., 2005;Jakymiw et al., 2005;Liu et al., 2005b;Pauley et al., 2006). miRNA-targeted mRNA also localizes to GWB in a miRNAdependent manner (Liu et al., 2005b). These observations provide the first evidence that RNAi is ...

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Section: Introductionmentioning

confidence: 99%

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

Lian¹,

Fritzler

Katz³

et al. 2007

MBoC

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“…However, putative RNA helicases and other cofactors that may target the exosome complex to its substrates have been identified. Several of the proteins required for these mRNA decay mechanisms have homologues in other eukaryotic cells, including mammals (Dangel et al, 1995;Lee et al, 1995;Bashkirov et al, 1997;Mitchell et al, 1997).…”

Section: Yeast Ski Complexmentioning

confidence: 99%

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

Bevilacqua

Ceriani

Capaccioli

et al. 2003

Journal Cellular Physiology

294

259

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Recent evidence suggests that gene expression may be regulated, at least in part, at post-transcriptional level by factors inducing the extremely rapid degradation of messenger RNAs. These factors include reactions between adenyl-uridyl-rich elements (AREs) of the relevant mRNA and either specific proteins that bind to these elements or exosomes. This review deals with examples of the proteins (AU-rich binding proteins, AUBPs) and exosomes, which have been shown to form complexes with AREs and bring about rapid degradation of the relevant mRNA, and with certain other factors, which protect the RNA from such degradation. The biochemical and physiological factors underlying the stability of messenger RNAs carrying the ARE motifs will be reviewed in the light of their emerging significance for cell physiology, human pathology, and molecular medicine. We also consider the possible application of the results of recent insights into the mechanisms to pharmacological interventions to prevent or cure disorders, especially developmental disorders, which the suppression of gene expression may bring about. Molecular targeting of specific steps in protein degradation by synthetic compounds has already been utilized for the development of pharmacological therapies.

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“…These data indicate that RNA guanine tetraplexes could be crucially involved in translational repression. Furthermore, RNA G tetraplexes have been reported to be specifically targeted by mammalian 5Ј-3Ј exoribonuclease (13), suggesting their potential role in mRNA turnover, which is important in determining the levels and regulation of gene expression. Despite the biological importance of RNA tetraplexes, their structural basis is not clear yet, and it could be much different from that of DNA tetraplexes.…”

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confidence: 99%

X-ray analysis of an RNA tetraplex (UGGGGU) ₄ with divalent Sr ²⁺ ions at subatomic resolution (0.61 Å)

Deng

Xiong²,

Sundaralingam³

2001

Proc. Natl. Acad. Sci. U.S.A.

143

106

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Four-stranded guanine tetraplexes in RNA have been identified to be involved in crucial biological functions, such as dimerization of retroviral RNA, translational repression, and mRNA turnover. However, the structural basis for these biological processes is still largely unknown. Here we report the RNA tetraplex structure (UGGGGU) 4 at ultra-high resolution (0.61 Å). The space group is P42 12, and cell constants are a ‫؍‬ b ‫؍‬ 36.16 Å and c ‫؍‬ 74.09 Å. The structure was solved by the multiple-wavelength anomalous dispersion method using a set of three-wavelength data of the isomorphous bromo derivative br UGGGGU and refined to 0.61-Å resolution. Each of the four strands in the asymmetric unit forms a parallel tetraplex with symmetry-related molecules. The tetraplex molecules stack on one another in opposite polarity (headto-head or tail-to-tail) to form a pseudocontinuous column. All of the 5 -end uridines rotate around the backbone of G2, swing out, and form unique octaplexes with the neighboring G tetraplexes, whereas the 3 -end uridines are stacked-in and form uridine tetrads. All of the bases are anti, and the riboses are in the mixed C2 -and C3 -puckering mode. Strontium ions are observed in every other guanine tetrad plane, sitting on the fourfold axis and associated to the eight O6 atoms of neighboring guanine bases in a bipyramidal-antiprism geometry. The hydrogens are clearly observed in the structure. ultra-high resolution ͉ uridine tetrad ͉ octad F or several decades, it has been known that guanine-rich repeats in nucleic acids can form four-stranded tetraplexes in the presence of monovalent ions (1-7) with various biological functions. For example, DNA guanine tetraplexes function in chromosome telomeres (8) and the site-specific recombination of immunoglobulin genes (9). The essential biological functions of RNA tetraplexes have been studied during the past several years. Intramolecular RNA G tetraplex was postulated for a guanine-rich segment adjacent to an endonucleolytic cleavage site in insulin-like growth factor II mRNA (10). Strong evidence has shown that interstrand RNA tetraplexes could be involved in dimerization of HIV 1 genomic RNA, which serves as a critical process in organization of genomic retroviral RNA into infectious virion particles (11). In addition, RNA G tetraplexes have recently been reported to be preferential substrates of bacteriophage fd gene 5 protein (12), which is responsible for the switch from double-stranded to single-stranded viral DNA replication after infection of the bacterial cell. These data indicate that RNA guanine tetraplexes could be crucially involved in translational repression. Furthermore, RNA G tetraplexes have been reported to be specifically targeted by mammalian 5Ј-3Ј exoribonuclease (13), suggesting their potential role in mRNA turnover, which is important in determining the levels and regulation of gene expression. Despite the biological importance of RNA tetraplexes, their structural basis is not clear yet, and it could be much different from ...

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A Mouse Cytoplasmic Exoribonuclease (mXRN1p) with Preference for G4 Tetraplex Substrates

Cited by 326 publications

References 75 publications

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

X-ray analysis of an RNA tetraplex (UGGGGU) ₄ with divalent Sr ²⁺ ions at subatomic resolution (0.61 Å)

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A Mouse Cytoplasmic Exoribonuclease (mXRN1p) with Preference for G4 Tetraplex Substrates

Cited by 326 publications

References 75 publications

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

Small Interfering RNA-mediated Silencing Induces Target-dependent Assembly of GW/P Bodies

Post‐transcriptional regulation of gene expression by degradation of messenger RNAs

X-ray analysis of an RNA tetraplex (UGGGGU) 4 with divalent Sr 2+ ions at subatomic resolution (0.61 Å)

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X-ray analysis of an RNA tetraplex (UGGGGU) ₄ with divalent Sr ²⁺ ions at subatomic resolution (0.61 Å)