The Experts below are selected from a list of 60057 Experts worldwide ranked by ideXlab platform
Joan A Steitz - One of the best experts on this subject based on the ideXlab platform.
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cell cycle control of microrna mediated Translation Regulation
Cell Cycle, 2008Co-Authors: Shobha Vasudevan, Yingchun Tong, Joan A SteitzAbstract:MicroRNAs are small regulatory RNA molecules that exert post-transcriptional control over expression of specific target mRNAs. AU-rich elements (AREs) are highly conserved 3′UTR sequences that alter the stability and Translation of mRNAs of clinical importance as a rapid and transient response to external and internal changes. We recently demonstrated that a reporter mRNA containing the tumor necrosis factor α (TNFα) ARE activates Translation in response to quiescence via microRNA target sites in the ARE. Further studies revealed that microRNAs in general have the potential to regulate Translation in a cell-cycle determined manner: in quiescent cells, microRNAs activate Translation while in cycling/proliferating cells, microRNAs repress Translation. In this study, we have analyzed microRNA Regulation of Translation at additional stages of the cell cycle. We observe the strongest repressive potential in the S and S/G2 phases with minimal repression in the G1 phase. Since asynchronously growing cells are pr...
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cell cycle control of microrna mediated Translation Regulation
Cell Cycle, 2008Co-Authors: Shobha Vasudevan, Yingchun Tong, Joan A SteitzAbstract:MicroRNAs are small regulatory RNA molecules that exert post-transcriptional control overexpression of specific target mRNAs. AU-rich elements (AREs) are highly conserved 3'UTR sequences that alter the stability and Translation of mRNAs of clinical importance as a rapid and transient response to external and internal changes. We recently demonstrated that a reporter mRNA containing the tumor necrosis factor alpha (TNFalpha) ARE activates Translation in response to quiescence via microRNA target sites in the ARE. Further studies revealed that microRNAs in general have the potential to regulate Translation in a cell cycle determined manner: in quiescent cells, microRNAs activate Translation while in cycling/proliferating cells, microRNAs repress Translation.
Adri A M Thomas - One of the best experts on this subject based on the ideXlab platform.
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the role of the 5 untranslated region of an mrna in Translation Regulation during development
The International Journal of Biochemistry & Cell Biology, 1999Co-Authors: Alike W Van Der Velden, Adri A M ThomasAbstract:Abstract Cap-dependent ribosomal scanning occurs on the majority of cellular 5′ UTRs. This process is severely hampered on long 5′ UTRs, containing AUGs and secondary structure. These characteristics are often found in mRNAs encoding regulatory proteins like proto-oncogenes, growth factors, their receptors, and homeodomain proteins. A number of these mRNAs use an alternative mechanism of Translation initiation, involving an internal ribosomal entry site (IRES). Cellular mRNAs containing a complex 5′ UTR or an IRES share an intriguing characteristic: their Translational efficiency can be very specifically regulated by their 5′ UTR, providing post-transcriptional Regulation. During embryonic development, the 5′ UTRs of Antp, Ubx, RARβ2, c-mos and c-myc regulate protein expression in a spatio-temporal manner. Translation initiation on a number of growth factor RNAs (IGFII, PDGF2, TGFβ, FGF-2, and VEGF) is specifically regulated during differentiation, growth, and stress. Furthermore, 5′ UTR activity, mutations in the 5′ UTR, or the occurrence of alternative 5′ UTRs have been implicated in the progression of various forms of cancer. The mechanisms involved in 5′ UTR mediated control are not well understood. Binding of trans -acting factors could mediate Translation stimulation or repression. Furthermore, the precise localization of upstream AUGs and the activity of the cap-binding initiation factor 4E are suggested to be important for Translation Regulation of these mRNAs. This review focuses on 5′ UTRs whose activity is regulated, the processes during which this Regulation occurs, and as far as known the mechanisms involved.
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the role of the 5 untranslated region of an mrna in Translation Regulation during development
The International Journal of Biochemistry & Cell Biology, 1999Co-Authors: Alike W Van Der Velden, Adri A M ThomasAbstract:Cap-dependent ribosomal scanning occurs on the majority of cellular 5' UTRs. This process is severely hampered on long 5' UTRs, containing AUGs and secondary structure. These characteristics are often found in mRNAs encoding regulatory proteins like proto-oncogenes, growth factors, their receptors, and homeodomain proteins. A number of these mRNAs use an alternative mechanism of Translation initiation, involving an internal ribosomal entry site (IRES). Cellular mRNAs containing a complex 5' UTR or an IRES share an intriguing characteristic: their Translational efficiency can be very specifically regulated by their 5' UTR, providing post-transcriptional Regulation. During embryonic development, the 5' UTRs of Antp. Ubx RAR beta 2 c-mos and c-myc regulate protein expression in a spatio-temporal manner. Translation initiation on a number of growth factor RNAs (IGFII, PDGF2, TGF beta, FGF-2, and VEGF) is specifically regulated during differentiation, growth, and stress. Furthermore, 5' UTR activity, mutations in the 5' UTR, or the occurrence of alternative 5' UTRs have been implicated in the progression of various forms of cancer. The mechanisms involved in 5' UTR mediated control are not well understood. Binding of trans-acting factors could mediate Translation stimulation or repression. Furthermore, the precise localization of upstream AUGs and the activity of the cap-binding initiation factor 4E are suggested to be important for Translation Regulation of these mRNAs. This review focuses on 5' UTRs whose activity is regulated, the processes during which this Regulation occurs, and as far as known the mechanisms involved.
Jean J Zhao - One of the best experts on this subject based on the ideXlab platform.
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targeted profiling of rna Translation reveals mtor 4ebp1 2 independent Translation Regulation of mrnas encoding ribosomal proteins
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Changli Qia, Thomas M Roberts, Jean J Zhao, Paulo A Gameiro, Chinchih Liu, Tao Jiang, Kevi StruhlAbstract:The PI3K-Akt-mTOR signaling pathway is a master regulator of RNA Translation. Pharmacological inhibition of this pathway preferentially and coordinately suppresses, in a 4EBP1/2-dependent manner, Translation of mRNAs encoding ribosomal proteins. However, it is unclear whether mechanistic target of rapamycin (mTOR)-4EBP1/2 is the exclusive Translation regulator of this group of genes, and furthermore, systematic searches for novel Translation modulators have been immensely challenging because of difficulties in scaling existing RNA Translation profiling assays. Here, we developed a rapid and highly scalable approach for gene-specific quantitation of RNA Translation, termed Targeted Profiling of RNA Translation (TPRT). We applied this technique in a chemical screen for Translation modulators, and identified numerous preclinical and clinical therapeutic compounds, with diverse nominal targets, that preferentially suppress Translation of ribosomal proteins. Surprisingly, some of these compounds act in a manner that bypasses canonical Regulation by mTOR-4EBP1/2. Instead, these compounds exert their Translation effects in a manner that is dependent on GCN2-eIF2α, a central signaling axis within the integrated stress response. Furthermore, we were also able to identify metabolic perturbations that also suppress ribosomal protein Translation in an mTOR-independent manner. Together, we describe a Translation assay that is directly applicable to large-scale RNA Translation studies, and that enabled us to identify a noncanonical, mTOR-independent mode for Translation Regulation of ribosomal proteins.
Ronald C. Wek - One of the best experts on this subject based on the ideXlab platform.
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Upstream Open Reading Frames Differentially Regulate Gene-specific Translation in the Integrated Stress Response.
Journal of Biological Chemistry, 2016Co-Authors: Sara K Young, Ronald C. WekAbstract:Abstract Translation Regulation largely occurs during initiation, which features ribosome assembly onto mRNAs and selection of the Translation start site. Short, upstream ORFs (uORFs) located in the 5′-leader of the mRNA can be selected for Translation. Multiple transcripts associated with stress amelioration are preferentially translated through uORF-mediated mechanisms during activation of the integrated stress response (ISR) in which phosphorylation of the α subunit of eIF2 results in a coincident global reduction in Translation initiation. This review presents key features of uORFs that serve to optimize Translational control that is essential for Regulation of cell fate in response to environmental stresses.
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Translation Regulation by eukaryotic initiation factor 2 kinases in the development of latent cysts in toxoplasma gondii
Journal of Biological Chemistry, 2008Co-Authors: Jana Narasimhan, Ronald C. Wek, Bradley R Joyce, Arunasalam Naguleswaran, Aaron T Smith, Meredith R Livingston, Stacy E Dixon, Isabelle Coppens, William J SullivanAbstract:A key problem in the treatment of numerous pathogenic eukaryotes centers on their development into latent forms during stress. For example, the opportunistic protist Toxoplasma gondii converts to latent cysts (bradyzoites) responsible for recrudescence of disease. We report that Toxoplasma eukaryotic initiation factor-2α (TgIF2α) is phosphorylated during stress and establish that protozoan parasites utilize Translation control to modulate gene expression during development. Importantly, TgIF2α remains phosphorylated in bradyzoites, explaining how these cells maintain their quiescent state. Furthermore, we have characterized novel eIF2 kinases; one in the endoplasmic reticulum and a likely regulator of the unfolded protein response (TgIF2K-A) and another that is a probable responder to cytoplasmic stresses (TgIF2K-B). Significantly, our data suggest that 1) the Regulation of protein Translation through eIF2 kinases is associated with development, 2) eIF2α phosphorylation is employed by cells to maintain a latent state, and 3) endoplasmic reticulum and cytoplasmic stress responses evolved in eukaryotic cells before the early diverging Apicomplexa. Given its importance to pathogenesis, eIF2 kinase-mediated stress responses may provide opportunities for novel therapeutics.
Shobha Vasudevan - One of the best experts on this subject based on the ideXlab platform.
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cell cycle control of microrna mediated Translation Regulation
Cell Cycle, 2008Co-Authors: Shobha Vasudevan, Yingchun Tong, Joan A SteitzAbstract:MicroRNAs are small regulatory RNA molecules that exert post-transcriptional control over expression of specific target mRNAs. AU-rich elements (AREs) are highly conserved 3′UTR sequences that alter the stability and Translation of mRNAs of clinical importance as a rapid and transient response to external and internal changes. We recently demonstrated that a reporter mRNA containing the tumor necrosis factor α (TNFα) ARE activates Translation in response to quiescence via microRNA target sites in the ARE. Further studies revealed that microRNAs in general have the potential to regulate Translation in a cell-cycle determined manner: in quiescent cells, microRNAs activate Translation while in cycling/proliferating cells, microRNAs repress Translation. In this study, we have analyzed microRNA Regulation of Translation at additional stages of the cell cycle. We observe the strongest repressive potential in the S and S/G2 phases with minimal repression in the G1 phase. Since asynchronously growing cells are pr...
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cell cycle control of microrna mediated Translation Regulation
Cell Cycle, 2008Co-Authors: Shobha Vasudevan, Yingchun Tong, Joan A SteitzAbstract:MicroRNAs are small regulatory RNA molecules that exert post-transcriptional control overexpression of specific target mRNAs. AU-rich elements (AREs) are highly conserved 3'UTR sequences that alter the stability and Translation of mRNAs of clinical importance as a rapid and transient response to external and internal changes. We recently demonstrated that a reporter mRNA containing the tumor necrosis factor alpha (TNFalpha) ARE activates Translation in response to quiescence via microRNA target sites in the ARE. Further studies revealed that microRNAs in general have the potential to regulate Translation in a cell cycle determined manner: in quiescent cells, microRNAs activate Translation while in cycling/proliferating cells, microRNAs repress Translation.
