Processing bodies require RNA for assembly and contain nontranslating mRNAs

Teixeira, Daniela; Sheth, Ujwal; Valencia-Sanchez, Marco Antonio; Brengues, Muriel; Parker, Roy

doi:10.1261/rna.7258505

Cited by 617 publications

(781 citation statements)

References 47 publications

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“…For example, the RNAi machinery as well as related cofactors, such as Argonaute proteins and GW182, are absent in Saccharomyces cerevisiae. The absence of RNAi in S. cerevisiae may explain the observed differences between yeast P bodies and mammalian P bodies (GWB) in responding to stresses (Sheth and Parker, 2003;Yang et al, 2004;Brengues et al, 2005;Teixeira et al, 2005). Yeast P bodies are considered sites for processing global messages, whereas GWB are more like specific cellular structures regulating and organizing siRNA/miRNA-mediated function.…”

Section: Regulation Of Gwb Assemblymentioning

confidence: 99%

“…Second, as sites for 5Ј33Ј mRNA decay, the size and number of GWB are affected by blocking deadenylation, decapping, and 5Ј33Ј mRNA degradation or translation (Sheth and Parker, 2003;Cougot et al, 2004;Andrei et al, 2005;Teixeira et al, 2005). GWB require RNA for assembly, and the amount of mRNA or mRNA decay intermediates accumulated in GWB affects the size and number of these foci (Sen and Blau, 2005;Brengues et al, 2005;Teixeira et al, 2005). Third, and more interestingly, our recent studies show that blocking the genesis of miRNA disassembles GWB and introducing siRNA into these cells reassembles these foci, implicating that either miRNA or the miRNA activities are crucial for the formation of GWB (Pauley et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…The majority of GWB disassembled before mitosis and small GWB reassembled in early G1 (Yang et al, 2004). Second, as sites for 5Ј33Ј mRNA decay, the size and number of GWB are affected by blocking deadenylation, decapping, and 5Ј33Ј mRNA degradation or translation (Sheth and Parker, 2003;Cougot et al, 2004;Andrei et al, 2005;Teixeira et al, 2005). GWB require RNA for assembly, and the amount of mRNA or mRNA decay intermediates accumulated in GWB affects the size and number of these foci (Sen and Blau, 2005;Brengues et al, 2005;Teixeira et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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: Regulation Of Gwb Assemblymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lian¹,

Fritzler

Katz³

et al. 2007

MBoC

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show abstract

“…For example, blocking translation initiation using mutations in initiation factors leads to an increase in the P-body size and number along with accelerated decay rates. Conversely, inhibition of translation elongation and trapping of the mRNAs in polysomes lead to the loss of P-bodies (Sheth and Parker 2003;Teixeira et al 2005). …”

mentioning

confidence: 99%

Stm1 Modulates mRNA Decay and Dhh1 Function in Saccharomyces cerevisiae

Balagopal

Parker

2009

Genetics

Self Cite

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The control of mRNA degradation and translation are important for the regulation of gene expression. mRNA degradation is often initiated by deadenylation, which leads to decapping and 59-39 decay. In the budding yeast Saccharomyces cerevisae, decapping is promoted by the Dhh1 and Pat1 proteins, which appear to both inhibit translation initiation and promote decapping. To understand the function of these factors, we identified the ribosome binding protein Stm1 as a multicopy suppressor of the temperature sensitivity of the pat1D strain. Stm1 loss-of-function alleles and overexpression strains show several genetic interactions with Pat1 and Dhh1 alleles in a manner consistent with Stm1 working upstream of Dhh1 to promote Dhh1 function. Consistent with Stm1 affecting Dhh1 function, stm1D strains are defective in the degradation of the EDC1 and COX17 mRNAs, whose decay is strongly affected by the loss of Dhh1. These results identify Stm1 as an additional component of the mRNA degradation machinery and suggest a possible connection of mRNA decapping to ribosome function.

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“…The targeted mRNA will be primarily subjected to translational repression, although mRNAs containing partial miRNA complementary sites may also be targeted for degradation in vivo (29). These regulatory events may occur at specific cytoplasmic foci referred to as processing bodies (P-bodies) (30,31), or GW182-containing bodies (GWbodies) (32), which are formed as a consequence of the presence of miRNAs (33). P-bodies are enriched in proteins involved in RNA-mediated gene silencing, such as Ago2 (30), mRNA degradation (34), and nonsense-mediated mRNA decay (35,36)…”

Section: The Endogenous Microrna-based Rna Silencing Machinerymentioning

confidence: 99%

Emergence of a Complex Relationship between HIV-1 and the microRNA Pathway

Ouellet¹,

Plante²,

Barat³

et al. 2008

Methods in Molecular Biology

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SummaryRecent experimental evidences support the existence of an increasingly complex and multifaceted interaction between viruses and the microRNA-guided RNA silencing machinery of human cells. The discovery of small interfering RNAs (siRNAs), which are designed to mediate cleavage of specific messenger RNAs (mRNAs), prompted virologists to establish therapeutic strategies based on siRNAs with the aim to suppress replication of several viruses, including human immunodeficiency virus type 1 (HIV-1). It has been appreciated only recently that viral RNAs can also be processed endogenously by the microRNA-generating enzyme Dicer or recognized by cellular miRNAs, in processes that could be viewed as an adapted antiviral defense mechanism. Known to repress mRNA translation through recognition of specific binding sites usually located in their 3′ untranslated region, miRNAs of host or viral origin may exert regulatory effects towards host and/or viral genes and influence viral replication and/or the host response to viral infection. This article summarizes our current state of knowledge on the relationship between HIV-1 and miRNA-guided RNA silencing, and discusses the different aspects of their interaction.

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Processing bodies require RNA for assembly and contain nontranslating mRNAs

Cited by 617 publications

References 47 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

Stm1 Modulates mRNA Decay and Dhh1 Function in Saccharomyces cerevisiae

Emergence of a Complex Relationship between HIV-1 and the microRNA Pathway

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