Translation (Austin, Tex.)最新文献_第10页

Clearance of yeast eRF-3 prion [PSI+] by amyloid enlargement due to the imbalance between chaperone Ssa1 and cochaperone Sgt2 由于伴侣Ssa1和伴侣Sgt2之间的不平衡，淀粉样蛋白增大对酵母eRF-3朊病毒[PSI+]的清除

Translation (Austin, Tex.) Pub Date : 2013-07-01 DOI: 10.4161/trla.26574

Chie Arai, H. Kurahashi, C. Pack, Y. Sako, Yoshikazu Nakamura

{"title":"Clearance of yeast eRF-3 prion [PSI+] by amyloid enlargement due to the imbalance between chaperone Ssa1 and cochaperone Sgt2","authors":"Chie Arai, H. Kurahashi, C. Pack, Y. Sako, Yoshikazu Nakamura","doi":"10.4161/trla.26574","DOIUrl":"https://doi.org/10.4161/trla.26574","url":null,"abstract":"The cytoplasmic [PSI+] element of budding yeast represents the prion conformation of translation release factor eRF-3 (Sup35). Prions are transmissible agents caused by self-seeded highly ordered aggregates (amyloids). Much interest lies in understanding how prions are developed and transmitted. However, the cellular mechanism involved in the prion clearance is unknown. Recently we have reported that excess misfolded multi-transmembrane protein, Dip5ΔC-v82, eliminates yeast prion [PSI+]. In this study, we showed that the prion loss was caused by enlargement of prion amyloids, unsuitable for transmission, and its efficiency was affected by the cellular balance between the chaperone Hsp70-Ssa1 and Sgt2, a small cochaperone known as a regulator of chaperone targeting to different types of aggregation-prone proteins. The present findings suggest that Sgt2 is titrated by excess Dip5ΔC-v82, and the shortage of Sgt2 led to non-productive binding of Ssa1 on [PSI+] amyloids. Clearance of prion [PSI+] by the imbalance between Ssa1 and Sgt2 might provide a novel array to regulate the release factor function in yeast.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84015585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Yeast telomere maintenance is globally controlled by programmed ribosomal frameshifting and the nonsense-mediated mRNA decay pathway. 酵母端粒的维持是由程序性核糖体移框和无义介导的mRNA衰变途径控制的。

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24418

Vivek M Advani, Ashton T Belew, Jonathan D Dinman

{"title":"Yeast telomere maintenance is globally controlled by programmed ribosomal frameshifting and the nonsense-mediated mRNA decay pathway.","authors":"Vivek M Advani, Ashton T Belew, Jonathan D Dinman","doi":"10.4161/trla.24418","DOIUrl":"https://doi.org/10.4161/trla.24418","url":null,"abstract":"<p><p>We have previously shown that ~10% of all eukaryotic mRNAs contain potential programmed -1 ribosomal frameshifting (-1 PRF) signals and that some function as mRNA destabilizing elements through the Nonsense-Mediated mRNA Decay (NMD) pathway by directing translating ribosomes to premature termination codons. Here, the connection between -1 PRF, NMD and telomere end maintenance are explored. Functional -1 PRF signals were identified in the mRNAs encoding two components of yeast telomerase, EST1 and EST2, and in mRNAs encoding proteins involved in recruiting telomerase to chromosome ends, STN1 and CDC13. All of these elements responded to mutants and drugs previously known to stimulate or inhibit -1 PRF, further supporting the hypothesis that they promote -1 PRF through the canonical mechanism. All affected the steady-state abundance of a reporter mRNA and the wide range of -1 PRF efficiencies promoted by these elements enabled the determination of an inverse logarithmic relationship between -1 PRF efficiency and mRNA accumulation. Steady-state abundances of the endogenous EST1, EST2, STN1 and CDC13 mRNAs were similarly inversely proportional to changes in -1 PRF efficiency promoted by mutants and drugs, supporting the hypothesis that expression of these genes is post-transcriptionally controlled by -1 PRF under native conditions. Overexpression of EST2 by ablation of -1 PRF signals or inhibition of NMD promoted formation of shorter telomeres and accumulation of large budded cells at the G2/M boundary. A model is presented describing how limitation and maintenance of correct stoichiometries of telomerase components by -1 PRF is used to maintain yeast telomere length. </p>","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/trla.24418","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32148454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 29

IRES-mediated translation of the pro-apoptotic Bcl2 family member PUMA ires介导的促凋亡Bcl2家族成员PUMA的翻译

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24391

Atossa Shaltouki, T. Harford, A. Komar, C. M. Weyman

{"title":"IRES-mediated translation of the pro-apoptotic Bcl2 family member PUMA","authors":"Atossa Shaltouki, T. Harford, A. Komar, C. M. Weyman","doi":"10.4161/trla.24391","DOIUrl":"https://doi.org/10.4161/trla.24391","url":null,"abstract":"The proapoptotic Bcl-2 family member PUMA is a critical regulator of apoptosis. We have previously shown that PUMA plays a pivotal role in the apoptosis associated with skeletal myoblast differentiation and that a MyoD-dependent mechanism is responsible for the increased expression of PUMA in these cells. Herein, we report that the increased expression of PUMA under these conditions involves regulation at the level of translation. Specifically, we have found that the increase in PUMA protein levels occurs under conditions of decreased total protein synthesis, eIF2-alpha phosphorylation and hypophosphorylation of eIF4E-BP, suggesting that PUMA translation is proceeding via an alternative initiation mechanism. Polyribosome analysis of PUMA mRNA further corroborated this suggestion. A combination of in vitro and ex vivo (cellular) approaches has provided evidence suggesting that PUMA mRNA 5'UTR harbors an Internal Ribosome Entry Site (IRES) element. Using mono- and bi-cistronic reporter constructs, we have delineated an mRNA fragment that allows for cap-independent translation in vitro and ex vivo (in skeletal myoblasts) in response to culture in differentiation media (DM), or in response to treatment with the DNA-damaging agent, etoposide. This mRNA fragment also supports translation in HeLa and 293T cells. Thus, our data has revealed a novel IRES-mediated regulation of PUMA expression in several cell types and in response to several stimuli. These findings contribute to our understanding and potential manipulation of any developmental or therapeutic scenario involving PUMA.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80980812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Introduction to Translation 翻译概论

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24611

V. Polunovsky, J. Hershey, N. Sonenberg

引用次数: 48

Physical evidence supporting a ribosomal shunting mechanism of translation initiation for BACE1 mRNA 物理证据支持BACE1 mRNA翻译起始的核糖体分流机制

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24400

D. C. Koh, G. Edelman, V. Mauro

{"title":"Physical evidence supporting a ribosomal shunting mechanism of translation initiation for BACE1 mRNA","authors":"D. C. Koh, G. Edelman, V. Mauro","doi":"10.4161/trla.24400","DOIUrl":"https://doi.org/10.4161/trla.24400","url":null,"abstract":"In Alzheimer disease, elevated levels of the BACE1 enzyme are correlated with increased production of amyloid peptides and disease pathology. The increase in BACE1 levels is post-transcriptional and may involve altered translation efficiency. Earlier studies have indicated that translation of BACE1 mRNA is cap-dependent. As ribosomal subunits move from the cap-structure to the initiation codon, they fail to recognize several AUG codons in the 5′ leader. In this study, we looked for physical evidence of the mechanism underlying ribosomal scanning or shunting along the BACE1 5′ leader by investigating structural stability in the 5′ leaders of endogenous mRNAs in vivo. To perform this analysis, we probed RNAs using lead(II) acetate, a cell-permeable chemical that induces cleavage of unpaired nucleotides having conformational flexibility. The data revealed that the ≈440-nt 5′ leader was generally resistant to cleavage except for a region upstream of the initiation codon. Cleavage continued into the coding region, consistent with destabilization of secondary structures by translating ribosomes. Evidence that a large segment of the BACE1 5′ leader was not cleaved indicates that this region is structurally stable and suggests that it is not scanned. The data support a mechanism of translation initiation in which ribosomal subunits bypass (shunt) part of the BACE1 5′ leader to reach the initiation codon. We suggest that a nucleotide bias in the 5′ leader may predispose the initiation codon to be more accessible than other AUG codons in the 5′ leader, leading to an increase in its relative utilization.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85597819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Translational control of the fibroblast-extracellular matrix association 成纤维细胞-细胞外基质关联的翻译控制

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.23934

R. Nho, V. Polunovsky

{"title":"Translational control of the fibroblast-extracellular matrix association","authors":"R. Nho, V. Polunovsky","doi":"10.4161/trla.23934","DOIUrl":"https://doi.org/10.4161/trla.23934","url":null,"abstract":"Pulmonary fibrosis is a severe lung disease characterized by sustained propagation of lung fibroblasts and relentless accumulation of extracellular matrix (ECM). Idiopathic pulmonary fibrosis (IPF) is the most severe chronic form of pulmonary fibrosis and results both in the gradual exchange of normal lung parenchyma with fibrotic tissue and in the irreversible impairment of gas exchange in the lung. Despite the urgency for novel therapies in IPF treatment, there is no effective and proven medical therapy available. Molecular mechanisms underlying IPF pathogenesis include aberrant ECM signaling through the canonical integrin/PI3K/Akt/mTORC1 signal transduction pathway. One important and well-characterized downstream effector of this pathway is the cellular protein synthesis machinery. Here we will review the recent advances in our understanding of the function of ECM and integrin receptor signaling in development of IPF and will present evidence indicating that the dysregulation of the eIF4F-mediated translational apparatus is an important factor in the development and progression of IPF and other fibrotic disorders. We further discuss the perspectives and challenges to curbing this deadly disease by targeting aberrant translation.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85920549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Eukaryotic initiation factor 4B and the poly(A)-binding protein bind eIF4G competitively 真核起始因子4B和聚(A)结合蛋白竞争性地结合eIF4G

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24038

Shijun Cheng, D. Gallie

{"title":"Eukaryotic initiation factor 4B and the poly(A)-binding protein bind eIF4G competitively","authors":"Shijun Cheng, D. Gallie","doi":"10.4161/trla.24038","DOIUrl":"https://doi.org/10.4161/trla.24038","url":null,"abstract":"The eukaryotic translation initiation factor (eIF) 4G functions as a scaffold protein that assembles components of the translation initiation complex required to recruit the 40S ribosomal subunit to an mRNA. Although many eukaryotes express two highly similar eIF4G isoforms, those in plants are highly divergent in size and sequence from one another and are referred to as eIF4G and eIFiso4G. Although the domain organization of eIFiso4G differs substantially from eIF4G orthologs in other species, the domain organization of plant eIF4G is largely unknown despite the fact that it is more similar in size and sequence to eIF4G of other eukaryotes. In this study, we show that eIF4G differs from eIFiso4G in that it contains two distinct interaction domains for the poly(A) binding protein (PABP) and eIF4B but is similar to eIFiso4G in having two eIF4A interaction domains. PABP and eIF4B bind the same N-terminal region of eIF4G as they do to a region C-proximal to the HEAT-1 domain in the middle domain of eIF4G, resulting in competitive binding between eIF4B and PABP to each site. eIF4G also differs from eIFiso4G in that no competitive binding was observed between PABP and eIF4A or between eIF4B and eIF4A to its HEAT-1-containing region. These results demonstrate that despite substantial differences in size, sequence, and domain organization, PABP and eIF4B bind to eIF4G and eIFiso4G competitively.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83587950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Fas-activated Ser/Thr phosphoprotein (FAST) is a eukaryotic initiation factor 4E-binding protein that regulates mRNA stability and cell survival fas激活的丝氨酸/苏氨酸磷酸化蛋白(FAST)是一种真核起始因子4e结合蛋白，调节mRNA的稳定性和细胞存活

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24047

Wei Li, P. Ivanov, P. Anderson

{"title":"Fas-activated Ser/Thr phosphoprotein (FAST) is a eukaryotic initiation factor 4E-binding protein that regulates mRNA stability and cell survival","authors":"Wei Li, P. Ivanov, P. Anderson","doi":"10.4161/trla.24047","DOIUrl":"https://doi.org/10.4161/trla.24047","url":null,"abstract":"The recognition of T cell intracellular antigen-1 (TIA-1) by Fas-activated Ser/Thr phosphoprotein (FAST) results in prolonged cell survival by inducing the expression of inhibitors of apoptosis. Here we show that the functional effects of FAST are dependent on its interactions with eukaryotic translation initiation factor 4E (eIF4E) which is the major cytosolic cap binding protein in cells. FAST binds to eIF4E via a consensus motif (428YXXXXLL433) that is also found in eIF4G, 4E-BP1/2/3, 4E-T, and cup. A point mutation within this motif at Y428 dampens the ability of FAST to recognize eIF4E. Wild-type (WT) FAST, but not its Y428G mutant, increases the expression of co-transfected cellular inhibitor of apoptosis-1 (cIAP-1) and β-gal mRNA and protein, but inhibits the Fas-induced activation of caspase-3. Increased expression of the co-transfected proteins results, in part, from stabilization of mRNA, suggesting that FAST:eIF4E interactions can inhibit mRNA decay. We propose that eIF4E:FAST:TIA-1 complexes regulate the translation and stability of specific mRNAs that encode proteins important for cell survival.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84135452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Influence of translation factor activities on start site selection in six different mRNAs 翻译因子活性对六种不同mrna起始位点选择的影响

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24419

Daine Barth-Baus, C. Bhasker, W. Zoll, W. Merrick

{"title":"Influence of translation factor activities on start site selection in six different mRNAs","authors":"Daine Barth-Baus, C. Bhasker, W. Zoll, W. Merrick","doi":"10.4161/trla.24419","DOIUrl":"https://doi.org/10.4161/trla.24419","url":null,"abstract":"Current literature using biochemical assays, structural analyses and genetic manipulations has reported that the key factors associated with the faithful matching of the initiator met-tRNA to the start codon AUG are eIF1, eIF1A and eIF5. However, these findings were in each case based upon the utilization of a single mRNA, perhaps with variations. In an effort to evaluate this general finding, we tested six different mRNAs. Our results confirm that these three proteins are important for start site selection. However, two additional findings would not have been predicted. The first is that eIF1 plays a major role in selecting against start codons that are in close proximity to the 5′ end of the mRNA (i.e., less than 21 nucleotides). Second, the addition of eIF5B had nearly the same affect as the addition of eIF5. This is unexpected given the different roles that eIF5 and eIF5B have been proposed to play in the 80S initiation pathway. Finally, although many of the mRNAs appear to respond qualitatively in a similar manner, the quantitative differences noted suggest that there is still some mRNA specific character to our findings. This character may be the length of the 5′ UTR, involvement of an IRES element, secondary structure either 5′ or 3′ of the start codon or specific sequence/structure elements that interact with RNA binding proteins or the ribosome.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78445831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

Dual use of GTP hydrolysis by elongation factor G on the ribosome 核糖体上延伸因子G水解GTP的双重用途

Translation (Austin, Tex.) Pub Date : 2013-04-01 DOI: 10.4161/trla.24315

C. E. Cunha, R. Belardinelli, F. Peske, W. Holtkamp, W. Wintermeyer, M. Rodnina

{"title":"Dual use of GTP hydrolysis by elongation factor G on the ribosome","authors":"C. E. Cunha, R. Belardinelli, F. Peske, W. Holtkamp, W. Wintermeyer, M. Rodnina","doi":"10.4161/trla.24315","DOIUrl":"https://doi.org/10.4161/trla.24315","url":null,"abstract":"Elongation factor G (EF-G) is a GTPase that catalyzes tRNA and mRNA translocation during the elongation cycle of protein synthesis. The GTP-bound state of the factor on the ribosome has been studied mainly with non-hydrolyzable analogs of GTP, which led to controversial conclusions about the role of GTP hydrolysis in translocation. Here we describe a mutant of EF-G in which the catalytic His91 is replaced with Ala. The mutant EF-G does not hydrolyze GTP, but binds GTP with unchanged affinity, allowing us to study the function of the authentic GTP-bound form of EF-G in translocation. Utilizing fluorescent reporter groups attached to the tRNAs, mRNA, and the ribosome we compile the velocity map of translocation seen from different perspectives. The data suggest that GTP hydrolysis accelerates translocation up to 30-fold and facilitates conformational rearrangements of both 30S subunit (presumably the backward rotation of the 30S head) and EF-G that lead to the dissociation of the factor. Thus, EF-G combines the energy regime characteristic for motor proteins, accelerating movement by a conformational change induced by GTP hydrolysis, with that of a switch GTPase, which upon Pi release switches the conformations of EF-G and the ribosome to low affinity, allowing the dissociation of the factor.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2013-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86867763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 66