Vertebrate mRNAs with a 5′-Terminal Pyrimidine Tract Are Candidates for Translational Repression in Quiescent Cells: Characterization of the Translational <i>cis</i>-Regulatory Element

Avni, Dror; Shama, Silvian; Loreni, Fabrizio; Meyuhas, Oded

doi:10.1128/mcb.14.6.3822-3833.1994

Cited by 14 publications

(10 citation statements)

References 78 publications

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“…The subset of eIF4E-sensitive mRNAs therefore probably depends on the cellular context, which influences the repertoire of expressed RBPs and mRNAs. Moreover, mTOR stimulates the translation of mRNAs with 5′ terminal oligopyrimidine tracts ('TOP mRNAs') that encode components of the translational machinery, including ribosomal proteins [53][54][55][56][57] . Under physiological conditions, however, the effects of mTOR on the translation of TOP mRNAs seem to be largely independent of the 4E-BPs 58 and eIF4E 59 .…”

Section: Genome-wide Organization Of Gene-expression Programsmentioning

confidence: 99%

Translational control of immune responses: from transcripts to translatomes

et al. 2014

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Selective translational control of gene expression is emerging as a principal mechanism for the regulation of protein abundance that determines a variety of functions in both the adaptive immune system and the innate immune system. The translation-initiation factor eIF4E acts as a node for such regulation, but non-eIF4E mechanisms are also prevalent. Studies of 'translatomes' (genome-wide pools of translated mRNA) have facilitated mechanistic discoveries by identifying key regulatory components, including transcription factors, that are under translational control. Here we review the current knowledge on mechanisms that regulate translation and thereby modulate immunological function. We further describe approaches for measuring and analyzing translatomes and how such powerful tools can facilitate future insights on the role of translational control in the immune system.

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Section: Genome-wide Organization Of Gene-expression Programsmentioning

confidence: 99%

Translational control of immune responses: from transcripts to translatomes

et al. 2014

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“…This result might be related to a weaker expression of the transgene in lymphoid versus myeloid cells due to the presence of the 5Ј noncoding region of the EGFP mRNA, which comprises a 5Ј-terminal oligopyrimidine tract (5Ј TOP) of the EF1␣ mRNA leader sequence. This cis-regulating element has been described as selectively repressing translation in quiescent cells [15] like lymphoid cells.…”

Section: Sustained In Vitro Egfp Expression In Transduced Cd34 + -Der...mentioning

confidence: 99%

Maximal Lentivirus-Mediated Gene Transfer and Sustained Transgene Expression in Human Hematopoietic Primitive Cells and Their Progeny

et al. 2002

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Gene therapy using permanent modifications of hematopoietic stem cells (HSC) has increasing potential applications for both genetic and acquired diseases. Considerable progress has been made recently in gene transfer to HSC by the use of lentivirus-derived vectors, which have the capacity to transduce noncycling cells. However, overall efficiency of HSC transduction reported so far is still not sufficient for numerous applications. We describe here an improved HSC transduction protocol, using the previously described lentiviral vector, that leads to more than 90% transduction of human CD34+ cells from cord blood, including NOD-LtSz-scid/scid repopulating cells. Moreover, under the same conditions, we transduce more than 75% and 80% of CD34+ cells mobilized in peripheral blood and from bone marrow, respectively. We further show that transgene expression is stable through time and hematopoietic cell differentiation in vitro as well as in vivo. Such a high HSC transduction efficiency opens new opportunities for both gene therapy applications and functional studies of regulator proteins of hematopoiesis.

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“…Terminal oligopyrimidine (TOP)‐containing mRNAs contain a motif following their 7‐methylguanosine triphosphate (m7 GTP) cap, which consists of an invariable C‐residue, followed by a 4–15 base pyrimidine tract containing a similar proportion of Cs and Us (Meyuhas & Kahan, ). A CG‐rich region is often found immediately downstream of the 5′ TOP motif and it is thought that in some cell types both the TOP motif and the CG‐rich region are required for full translational control (Avni, Biberman, & Meyuhas, ; Avni, Shama, Loreni, & Meyuhas, ). Studies to identify the number of TOP‐containing mRNAs have suggested that there are 93 such mRNAs including 79 out of 80 ribosomal proteins, all five translation elongation factors ( EEF1A1 , EEF1B2 , EEF1D , EEF1G , and EEF2 ), translation initiation factors (eIF3e, eIF3f, eIF4B, and eIF3h), poly(A) binding protein (PABPC1), nucleophosmin (NPM1), receptor of activated protein C kinase 1 (Rack1/GNB2L1), translationally‐controlled tumor protein 1 (TPT1), polypyrimidine tract‐binding protein 1 (PTPB1/HNRNP1), nucleosome assembly protein 1‐like 1 (NAP1L1) and vimentin (VIM; Horvilleur et al, ; Iadevaia, Caldarola, Tino, Amaldi, & Loreni, ; Meyuhas & Kahan, ; Yoshihama et al, ).…”

Section: Rna‐binding Domainsmentioning

confidence: 99%

Trans‐acting translational regulatory RNA binding proteins

et al. 2018

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The canonical molecular machinery required for global mRNA translation and its control has been well defined, with distinct sets of proteins involved in the processes of translation initiation, elongation and termination. Additionally, noncanonical, trans‐acting regulatory RNA‐binding proteins (RBPs) are necessary to provide mRNA‐specific translation, and these interact with 5′ and 3′ untranslated regions and coding regions of mRNA to regulate ribosome recruitment and transit. Recently it has also been demonstrated that trans‐acting ribosomal proteins direct the translation of specific mRNAs. Importantly, it has been shown that subsets of RBPs often work in concert, forming distinct regulatory complexes upon different cellular perturbation, creating an RBP combinatorial code, which through the translation of specific subsets of mRNAs, dictate cell fate. With the development of new methodologies, a plethora of novel RNA binding proteins have recently been identified, although the function of many of these proteins within mRNA translation is unknown. In this review we will discuss these methodologies and their shortcomings when applied to the study of translation, which need to be addressed to enable a better understanding of trans‐acting translational regulatory proteins. Moreover, we discuss the protein domains that are responsible for RNA binding as well as the RNA motifs to which they bind, and the role of trans‐acting ribosomal proteins in directing the translation of specific mRNAs.This article is categorized under: RNA Interactions with Proteins and Other Molecules > RNA–Protein ComplexesTranslation > Translation RegulationTranslation > Translation Mechanisms

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Vertebrate mRNAs with a 5′-Terminal Pyrimidine Tract Are Candidates for Translational Repression in Quiescent Cells: Characterization of the Translational cis-Regulatory Element

Cited by 14 publications

References 78 publications

Translational control of immune responses: from transcripts to translatomes

Translational control of immune responses: from transcripts to translatomes

Maximal Lentivirus-Mediated Gene Transfer and Sustained Transgene Expression in Human Hematopoietic Primitive Cells and Their Progeny

Trans‐acting translational regulatory RNA binding proteins

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