Differential contribution of the m7G-cap to the 5′ end-dependent translation initiation of mammalian mRNAs
Dmitri E. Andreev,Sergey E. Dmitriev,Ilya M. Terenin,Vladimir S. Prassolov,William C. Merrick,Ivan N. Shatsky +5 more
TLDR
It is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated, because in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5′ UTRs.Abstract:
Many mammalian mRNAs possess long 5' UTRs with numerous stem-loop structures. For some of them, the presence of Internal Ribosome Entry Sites (IRESes) was suggested to explain their significant activity, especially when cap-dependent translation is compromised. To test this hypothesis, we have compared the translation initiation efficiencies of some cellular 5' UTRs reported to have IRES-activity with those lacking IRES-elements in RNA-transfected cells and cell-free systems. Unlike viral IRESes, the tested 5' UTRs with so-called 'cellular IRESes' demonstrate only background activities when placed in the intercistronic position of dicistronic RNAs. In contrast, they are very active in the monocistronic context and the cap is indispensable for their activities. Surprisingly, in cultured cells or cytoplasmic extracts both the level of stimulation with the cap and the overall translation activity do not correlate with the cumulative energy of the secondary structure of the tested 5' UTRs. The cap positive effect is still observed under profound inhibition of translation with eIF4E-BP1 but its magnitude varies for individual 5' UTRs irrespective of the cumulative energy of their secondary structures. Thus, it is not mandatory to invoke the IRES hypothesis, at least for some mRNAs, to explain their preferential translation when eIF4E is partially inactivated.read more
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Conflict of interest statement. None declared.
TL;DR: It is found that women over 50 are more likely to have a family history of diabetes, especially if they are obese, than women under the age of 50.
Journal ArticleDOI
Cellular IRES-mediated translation: the war of ITAFs in pathophysiological states.
Anton A. Komar,Maria Hatzoglou +1 more
TL;DR: This review presents examples in which the competitive action of IRES-transacting factors plays a pivotal role in IRes-mediated translation and thereby controls cell-fate decisions leading to either pro-survival stress adaptation or cell death.
Journal ArticleDOI
SARS Coronavirus nsp1 Protein Induces Template-Dependent Endonucleolytic Cleavage of mRNAs: Viral mRNAs Are Resistant to nsp1-Induced RNA Cleavage
Cheng Huang,Kumari G. Lokugamage,Janet M. Rozovics,Krishna Narayanan,Bert L. Semler,Shinji Makino +5 more
TL;DR: It is revealed that the nsp1 induced endonucleolytic RNA cleavage mainly near the 5′ untranslated region of capped mRNA templates, which may be an important strategy by which the virus circumvents the action of nsp 1 leading to the efficient accumulation of viral mRNAs and viral proteins during infection.
Journal ArticleDOI
Translation of 5' leaders is pervasive in genes resistant to eIF2 repression
Dmitry E. Andreev,Patrick B F O'Connor,Ciara Fahey,Elaine Kenny,Ilya M. Terenin,Sergey E. Dmitriev,Paul Cormican,Derek W. Morris,Ivan N. Shatsky,Pavel V. Baranov +9 more
TL;DR: Phylogenetic analysis suggests that at least two regulatory uORFs in SLC35A4 and MIEF1 encode functional protein products, and site-specific mutagenesis of two identified stress resistant mRNAs demonstrated that a single uORF is sufficient for eIF2-mediated translation control in both cases.
Journal ArticleDOI
eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation
TL;DR: The results reveal a mechanism of cap-dependent translation that is independent of eIF4E, and illustrate how modular RNA elements work together to direct specialized forms of translation initiation, and reveal unexpected homology to endonucleases involved in RNA turnover.
References
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Journal ArticleDOI
The scanning model for translation: an update.
TL;DR: The small (40S) subunit of eukaryotic ribosomes is believed to bind initially at the capped 5'-end of messenger RNA and then migrate, stopping at the first AUG codon in a favorable context for initiating translation.
Journal ArticleDOI
Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA
Jerry Pelletier,Nahum Sonenberg +1 more
TL;DR: A novel mechanism of initiation on poliovirus RNA occurs by binding of ribosomes to an internal sequence within the 5′ noncoding region, which may explain the disparate translation of several other eukaryotic messenger RNAs.
Conflict of interest statement. None declared.
TL;DR: It is found that women over 50 are more likely to have a family history of diabetes, especially if they are obese, than women under the age of 50.
Journal ArticleDOI
Translational control in stress and apoptosis
Martin Holcik,Nahum Sonenberg +1 more
TL;DR: Two representative models are examined, the regulation of eukaryotic initiation factor-2α by phosphorylation and internal ribosome initiation through the internal Ribosome-entry site, which illustrate the importance of translational control in the cellular stress response and apoptosis.
Journal ArticleDOI
Molecular mechanisms of translation initiation in eukaryotes.
Tatyana V. Pestova,Victoria G. Kolupaeva,Ivan B. Lomakin,Evgeny V. Pilipenko,Ivan N. Shatsky,Vadim I. Agol,Christopher U.T. Hellen +6 more
TL;DR: Encephalomyocarditis virus (EMCV) and hepatitis C virus epitomize distinct mechanisms of internal ribosomal entry site (IRES)-mediated initiation, and initiation on some EMCV-like IRESs requires additional noncanonical initiation factors, which alter IRES conformation and promote binding of eIF4A/4G.
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