Translation (Austin, Tex.)最新文献_第9页

Co-translational mechanisms of quality control of newly synthesized polypeptides 新合成多肽质量控制的共翻译机制

Translation (Austin, Tex.) Pub Date : 2014-01-01 DOI: 10.4161/trla.28109

V. Gandin, I. Topisirovic

引用次数: 10

Internal translation initiation from HIV-1 transcripts is conferred by a common RNA structure HIV-1转录本的内部翻译起始是由一个共同的RNA结构赋予的

Translation (Austin, Tex.) Pub Date : 2014-01-01 DOI: 10.4161/trla.27694

Terra-Dawn M. Plank, James T. Whitehurst, R. Cencic, J. Pelletier, J. Kieft

引用次数: 15

Targeting translation initiation in breast cancer 靶向乳腺癌翻译起始

Translation (Austin, Tex.) Pub Date : 2014-01-01 DOI: 10.4161/trla.28968

A. Akcakanat, D. Hong, F. Meric-Bernstam

引用次数: 3

An AU-rich instability element in the 3′UTR mediates an increase in mRNA stability in response to expression of a dhh1 ATPase mutant 3'UTR中富含au的不稳定元件介导mRNA稳定性的增加，以响应dhh1 atp酶突变体的表达

Translation (Austin, Tex.) Pub Date : 2014-01-01 DOI: 10.4161/trla.28587

S. Kramer, M. Carrington

{"title":"An AU-rich instability element in the 3′UTR mediates an increase in mRNA stability in response to expression of a dhh1 ATPase mutant","authors":"S. Kramer, M. Carrington","doi":"10.4161/trla.28587","DOIUrl":"https://doi.org/10.4161/trla.28587","url":null,"abstract":"The DEAD box RNA helicase DHH1 acts as a general repressor of translation and activator of decapping but can also act specifically on individual mRNAs. In trypanosomes, DHH1 overexpression or expression of a dhh1 ATPase mutant, dhh1 DEAD:DQAD, resulted in increased or decreased stability of a small group of mRNAs, mainly encoding developmentally regulated genes. Here, four of the mRNAs affected by dhh1 DEAD:DQAD expression have been analyzed to identify cis-elements involved in dhh1 DEAD:DQAD action. For three mRNAs, the 3′ UTR mediated the change in mRNA level and, in one case, both the 5′ and the 3′ UTR contributed. No responsive elements were detected in the protein coding sequences. One mRNA stabilized by dhh1 DEAD:DQAD expression was analyzed in more detail: deletion or mutation of an AU-rich element in the 3′ UTR resulted in mRNA stabilization in the absence of dhh1 DEAD:DQAD and completely abolished the response to dhh1 DEAD:DQAD. While AU-rich instability elements have been previously shown to mediate mRNA decrease or translational exit by recruitment of DHH1, this is, to our knowledge, the first report of an AU-rich instability element that is responsible for a DHH1 mediated increase in mRNA stability. We suggest a novel model for the selective action of dhh1 on individual mRNAs that is based on the change in the turnover rate of stabilizing or destabilizing RNA binding proteins.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87052090","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: 3

Recent transcriptome-wide mapping of UPF1 binding sites reveals evidence for its recruitment to mRNA before translation. 最近对UPF1结合位点的全转录组图谱揭示了其在翻译前向mRNA募集的证据。

Translation (Austin, Tex.) Pub Date : 2013-10-31 eCollection Date: 2013-01-01 DOI: 10.4161/trla.26977

David Zünd, Oliver Mühlemann

引用次数: 0

Random mutagenesis of yeast 25S rRNA identify bases critical for 60S subunit structural integrity and function 酵母25S rRNA随机突变鉴定60S亚基结构完整性和功能的关键碱基

Translation (Austin, Tex.) Pub Date : 2013-07-01 DOI: 10.4161/trla.26402

N. Nemoto, T. Udagawa, Wasimul Q. Chowdhury, M. Kitabatake, Byung-shik Shin, H. Hiraishi, Suzhi Wang, C. R. Singh, Susan J. Brown, M. Ohno, K. Asano

{"title":"Random mutagenesis of yeast 25S rRNA identify bases critical for 60S subunit structural integrity and function","authors":"N. Nemoto, T. Udagawa, Wasimul Q. Chowdhury, M. Kitabatake, Byung-shik Shin, H. Hiraishi, Suzhi Wang, C. R. Singh, Susan J. Brown, M. Ohno, K. Asano","doi":"10.4161/trla.26402","DOIUrl":"https://doi.org/10.4161/trla.26402","url":null,"abstract":"In yeast Saccharomyces cerevisiae, 25S rRNA makes up the major mass and shape of the 60S ribosomal subunit. During translation initiation, the 60S subunit joins the 40S initiation complex, producing the 80S initiation complex. During elongation, the 60S subunit binds the CCA-ends of aminoacyl- and peptidyl-tRNAs at the A-loop and P-loop, respectively, transferring the peptide onto the α-amino group of the aminoacyl-tRNA. To study the role of 25S rRNA in translation in vivo, we randomly mutated 25S rRNA and isolated and characterized seven point mutations that affected yeast cell growth and polysome profiles. Four of these mutations, G651A, A1435U, A1446G and A1587G, change a base involved in base triples crucial for structural integrity. Three other mutations change bases near the ribosomal surface: C2879U and U2408C alter the A-loop and P-loop, respectively, and G1735A maps near a Eukarya-specific bridge to the 40S subunit. By polysome profiling in mmslΔ mutants defective in nonfunctional 25S rRNA decay, we show that some of these mutations are defective in both the initiation and elongation phases of translation. Of the mutants characterized, C2879U displays the strongest defect in translation initiation. The ribosome transit-time assay directly shows that this mutation is also defective in peptide elongation/termination. Thus, our genetic analysis not only identifies bases critical for structural integrity of the 60S subunit, but also suggests a role for bases near the peptidyl transferase center in translation initiation.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78224133","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: 4

In silico motif analysis suggests an interplay of transcriptional and translational control in mTOR response 硅基序分析表明mTOR反应中转录和翻译控制的相互作用

Translation (Austin, Tex.) Pub Date : 2013-07-01 DOI: 10.4161/trla.27469

I. Eliseeva, I. Vorontsov, Kirill Babeyev, S. Buyanova, Maria Sysoeva, F. Kondrashov, I. Kulakovskiy

{"title":"In silico motif analysis suggests an interplay of transcriptional and translational control in mTOR response","authors":"I. Eliseeva, I. Vorontsov, Kirill Babeyev, S. Buyanova, Maria Sysoeva, F. Kondrashov, I. Kulakovskiy","doi":"10.4161/trla.27469","DOIUrl":"https://doi.org/10.4161/trla.27469","url":null,"abstract":"The short 5'-terminal oligopyrimidine tract (TOP) of 5' UTRs is a well-known regulatory sequence motif of mRNAs that are subject to growth-dependent translation. Specifically, translation of TOP mRNAs is regulated by the mTOR signaling pathway that is involved in cell proliferation, cancer development and aging. High throughput data permit detailed study of specific features of the mRNA TOP motif and its DNA origins at transcription start sites (TSS). Recently, ribosome profiling was used to identify mRNA targets of the mTOR pathway in PC3 cells. A novel pyrimidine-rich translational element (PRTE) was reported to play a key role without positional preferences within the 5' UTRs, unlike 5' TOP, which are strictly located at the 5' ends. In this study, we couple recently reported ribosome profiling data on the mTOR mRNA targets with the annotation of TSS obtained by HeliScopeCAGE. We confirm the canonical TOP and strong positional preferences of respective oligopyrimidine tracts (OP) straddling the experimentally validated TSS regions at the DNA level. Such OP localization ensures that transcription from OP segments creates the 5'-terminal TOP in the corresponding mRNAs. We demonstrate that OP are not overrepresented in downstream regions of 5' UTRs of mTOR targets. Finally, we highlight several mTOR target genes with broad and multimodal TSS spanning dozens of nucleotides that are only partically covered with an OP. Therefore, in such cases only a fraction of all produced mRNAs carry a TOP regulatory motif and, thus, respond to mTOR via TOP mechanism. We hypothesize that the interplay between transcription and translation may play a crucial role in the regulation of the mTOR response.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80257703","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: 11

Cap dependent translation contributes to resistance of myeloma cells to bortezomib 帽依赖翻译有助于骨髓瘤细胞对硼替佐米的抗性

Translation (Austin, Tex.) Pub Date : 2013-07-01 DOI: 10.4161/trla.27245

Marilena Mancino, S. Grosso, C. Terragna, E. Borsi, M. Cavo, S. Biffo

{"title":"Cap dependent translation contributes to resistance of myeloma cells to bortezomib","authors":"Marilena Mancino, S. Grosso, C. Terragna, E. Borsi, M. Cavo, S. Biffo","doi":"10.4161/trla.27245","DOIUrl":"https://doi.org/10.4161/trla.27245","url":null,"abstract":"Multiple myeloma (MM) is the second most predominant blood malignancy. Proteasome inhibitors like bortezomib have increased life expectancy, but eventually patients develop resistance to therapy. It was proposed that bortezomib acts through the induction of the Unfolded Protein Response (UPR), i.e., accumulation of misfolded proteins causing a lethal stress response. By this theory, increasing the proteasome load by the stimulation of translation may worsen the UPR. Here we evaluated the crosstalk between translation and bortezomib toxicity in both bortezomib sensitive and resistant cells. We found that bortezomib toxicity does not correlate with induction of proapoptotic eIF2α phosphorylation, but rather caused a late reduction in initiation of translation. This effect was accompanied by dephosphorylation of the mTORC1 target 4E-BP1. Infection of myeloma cells with constitutively dephosphorylated 4E-BP1, worsened bortezomib induced cell death. Since mTORC1 inhibitors cause pharmacological inhibition of 4E-BP1 phosphorylation, we tested whether they could act synergistically with bortezomib. We found that both rapamycin, a specific mTORC1 blocker, and PP242 a mTOR antagonist induce the arrest of myeloma cells irrespective of bortezomib sensitivity. Sensitivity to mTOR inhibitors has been associated to the levels of eIF4E/4E-BPs. We found that levels of eIF4E and 4E-BPs are variable among patients, and that 15% of myeloma patients have increased levels of 4E-BP1/2. Primary cells of myeloma retain sensitivity to mTOR inhibition, when plated on stromal cells. We propose that translational load does not contribute to bortezomib-induced death, but rather mTOR targeting may be successful in bortezomib resistant patients, stratified for eIF4E/4EBPs.","PeriodicalId":90376,"journal":{"name":"Translation (Austin, Tex.)","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78321004","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

4E-BP restrains eIF4E phosphorylation 4E-BP抑制eIF4E磷酸化

Translation (Austin, Tex.) Pub Date : 2013-07-01 DOI: 10.4161/trla.25819

D. Müller, C. Lasfargues, Sally El Khawand, A. Alard, R. Schneider, C. Bousquet, S. Pyronnet, Y. Martineau

引用次数: 29

PUNCH-P for global translatome profiling PUNCH-P用于全局翻译组分析

Translation (Austin, Tex.) Pub Date : 2013-07-01 DOI: 10.4161/trla.27516

Ranen Aviner, T. Geiger, O. Elroy-Stein

引用次数: 11