CA Repeats in the 3′-Untranslated Region of bcl-2 mRNA Mediate Constitutive Decay of bcl-2 mRNA

Lee, Jung‐Hee; Jeon, Mi-Hee; Seo, Yun-Jee; Lee, Yong-Joon; Ko, Jeong Heon; Tsujimoto, Yoshihide; Lee, Jeong-Hwa

doi:10.1074/jbc.m407357200

Cited by 27 publications

(23 citation statements)

References 32 publications

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“…This diversity presumably arises from the diverse RNA-binding factors and the diverse RNA-protein and protein-protein interactions in the decay machinery (8-11). Many cis-acting elements and trans-acting factors have been shown to engage in mRNA turnover regulation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In mammalian cells, the most common cis element is the AU-rich element (ARE) (21-24), which has been found in the 3Ј UTR of a wide variety of short-lived mRNAs, such as those of growth factors, cytokines, and protooncogenes (25-27).…”

Section: Rna Degradationmentioning

confidence: 99%

The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA

Guo

Ma²,

Sun³

et al. 2007

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

258

262

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Zinc-finger antiviral protein (ZAP) is a host antiviral factor that specifically inhibits the replication of Moloney murine leukemia virus (MLV) and Sindbis virus (SIN) by preventing accumulation of the viral mRNA in the cytoplasm. In previous studies, we demonstrated that ZAP directly binds to its specific target mRNAs. In this article, we provide evidence indicating that ZAP recruits the RNA processing exosome to degrade the target RNA. ZAP comigrated with the exosome in sucrose or glycerol velocity gradient centrifugation. Immunoprecipitation of ZAP coprecipitated the exosome components. In vitro pull-down assays indicated that ZAP directly interacted with the exosome component hRrp46p and that the binding region of ZAP was mapped to amino acids 224 -254. Depletion of the exosome component hRrp41p or hRrp46p with small interfering RNA significantly reduced ZAP's destabilizing activity. These findings suggest that ZAP is a trans-acting factor that modulates mRNA stability. RNA degradationT he degradation of mRNA is an important control point in the regulation of gene expression (1-6). The general mRNA decay is initiated by removal of the poly(A) tail. The body of the RNA is degraded either from the 5Ј end by exonuclease Xrn1 after decapping or from the 3Ј end by an exoribonucleases complex named the exosome (7).RNA decay mechanisms are diverse in the extent of decay and decay characteristics. This diversity presumably arises from the diverse RNA-binding factors and the diverse RNA-protein and protein-protein interactions in the decay machinery (8-11). Many cis-acting elements and trans-acting factors have been shown to engage in mRNA turnover regulation (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In mammalian cells, the most common cis element is the AU-rich element (ARE) (21-24), which has been found in the 3Ј UTR of a wide variety of short-lived mRNAs, such as those of growth factors, cytokines, and protooncogenes (25-27). Various ARE binding proteins (AUBPs) have been shown to modulate the stability of ARE-containing RNAs. Some AUBPs such as HuR (13, 28) and NF90 (29) stabilize the RNA, and other AUBPs such as tristetraprolin (TTP) (12,30,31), KRSP (32), and AUF1 (33, 34) destabilize the RNA. It has been reported that the destabilizing AUBPs recruit the exosome to degrade the ARE-containing RNAs (35).The exosome is an evolutionarily highly conserved 3Ј-5Ј exoribonucleases complex existing in both the nucleus and the cytoplasm (36-40). The nuclear exosome is required for the 3Ј processing of many RNA substrates, including prerRNA, snoRNA, snRNA, and premRNA (41-43). The nuclear exosome also functions in the surveillance system, in which the transcripts with defects generated in the RNA processing and exporting pathways are degraded (44-46). The cytoplasmic exosome plays a key role in the degradation of aberrant or unused intermediate mRNAs and AREcontaining mRNAs (1,35,(47)(48)(49)(50)(51)(52)(53). The effects on the target RNA depend on interactions among the exosome, exosome cofactors, the target RNA, and sp...

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Section: Rna Degradationmentioning

confidence: 99%

The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA

Guo

Ma²,

Sun³

et al. 2007

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

258

262

View full text Add to dashboard Cite

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“…In mammalian cells, the 3Ј-5Ј pathway is the major pathway (21,22). A variety of cis-acting motifs can promote mRNA degradation (23)(24)(25)(26)(27). ZAP directly binds to one such element, the ZRE, and recruits the exosome to degrade the ZRE-containing mRNA (5,6).…”

Section: Discussionmentioning

confidence: 99%

p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein

Chen

Guo

et al. 2008

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

102

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The zinc-finger antiviral protein (ZAP) specifically inhibits the replication of many viruses by preventing the accumulation of viral mRNAs in the cytoplasm. ZAP directly binds to the viral mRNAs and recruits the RNA exosome to degrade the target RNA. In the present study, we identified the p72 DEAD box RNA helicase, but not the highly similar RNA helicase p68, as a ZAP-interacting protein. The binding domain of ZAP was mapped to its N-terminal portion, whereas both the N-and C-terminal domains of p72 bound to ZAP. Overexpression of the C-terminal domain of p72 reduced ZAP's activity, whereas overexpression of the full-length p72 enhanced ZAP's activity. The RNA helicase activity was required for p72 to promote ZAP-mediated RNA degradation. Depletion of p72 by RNAi also reduced ZAP's activity but did not affect tristetraprolin-mediated RNA degradation. We conclude that p72 is required for the optimal activity of ZAP, and we propose that p72 helps to restructure the ZAP-bound target mRNA for efficient degradation.restriction ͉ RNA degredation ͉ retrovirus ͉ alphavirus T he zinc-finger antiviral protein (ZAP) was initially recovered as a host factor that inhibited the infection of cells by Moloney murine leukemia virus (MLV) (1). In addition to MLV, overexpression of ZAP also inhibits the replication of Ebola virus and Marburg virus (2), and several members of the Alphavirus genus, including Sindbis virus (SINV) (3). IFN treatment or SINV infection of murine bone marrow-derived dendritic cells significantly up-regulates the expression level of ZAP (4), suggesting that ZAP also may function as an antiviral effector in vivo. However, ZAP is not a universal antiviral factor; some viruses, including herpes simplex virus type 1 and yellow fever virus, grow normally in ZAP-expressing cells (3).ZAP inhibits virus replication by preventing the accumulation of the viral mRNA in the cytoplasm (1-3). In the N terminus of ZAP, there are four CCCH-type zinc-finger motifs (1). ZAP directly binds to specific viral mRNA sequences [ZAPresponsive element (ZRE)] through the CCCH-type zinc fingers (5). Furthermore, ZAP directly interacts with the RNAprocessing exosome (6), a 3Ј-5Ј exoribonucleases complex consisting of at least nine components (7). The current working model is that ZAP promotes the degradation of ZRE-containing mRNAs by directly binding to the target RNA and recruiting the exosome to degrade the RNA (6).The p72 RNA helicase is a member of the DEAD box family of RNA helicases, which are characterized by a conserved motif including Asp-Glu-Ala-Asp (DEAD) and involved in various biological processes (8,9). Compared with other DEAD box RNA helicases, p72 has a unique N-terminal domain containing repeats of the sequence RGG and a C-terminal domain rich in serine and glycine and terminating with a polyproline region (10). p72 is highly related to the better known p68 RNA helicase; they share Ϸ90% sequence identity in the core region spanning the conserved motifs characteristic of this family and 69.7% overall homology (10)...

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“…A further possibility of BMP effects on regulation of NGF-activated transcripts in the PC12 cells is controlling mRNA stability (19,20). We directly measured the half-life of Egr3 and Junb mRNA transcripts in the PC12 cells after 1 h of NGF stimulation (data not shown).…”

Section: Egr3 Promoter Activity In Response To Ngf and Bmp4mentioning

confidence: 97%

BMP Enhances Transcriptional Responses to NGF During PC12 Cell Differentiation

et al. 2005

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Bone morphogenetic proteins (BMPs) enhance neurite outgrowth in nerve growth factor (NGF)-stimulated PC12 cells. To investigate the mechanism of this potentiating effect, real-time PCR was used to analyze the expression of 45 selected genes. A robust increase in expression of 10 immediate early genes including Egr1-4, Hes1, Junb, Jun and Fos was observed already after 1 h treatment with NGF alone. NGF plus BMP4 further increased these transcripts at 1 h and activated 18 additional genes. BMP4 alone induced Smad6, Mtap1b and Hes1. Egr3 was the gene most strongly upregulated by NGF and BMP4. However, luciferase assays showed that the cloned Egr3 proximal promoter was not involved in the BMP4 potentiation. Blocking Egr3 and Junb function by dominant-negative constructs reduced neurite outgrowth under stimulating conditions, proving that activation of members of both the Egr and Jun families is necessary for maximal PC12 cell response to NGF and BMP4.

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CA Repeats in the 3′-Untranslated Region of bcl-2 mRNA Mediate Constitutive Decay of bcl-2 mRNA

Cited by 27 publications

References 32 publications

The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA

The zinc-finger antiviral protein recruits the RNA processing exosome to degrade the target mRNA

p72 DEAD box RNA helicase is required for optimal function of the zinc-finger antiviral protein

BMP Enhances Transcriptional Responses to NGF During PC12 Cell Differentiation

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