Trends in Biochemical Sciences
Translational control by the 3′-UTR: the ends specify the means
Section snippets
Translational control mechanisms
We are beginning to understand the control processes and molecular mechanisms that regulate translation. Translational regulation can be subdivided into two groups, global and transcript-specific control. Global control enables vertebrate cells to utilize strategies that offer temporal, and possibly spatial, co-regulation of many, or most, expressed transcripts. Such control is used in cellular responses to a threatening stress, such as viral infection, ultraviolet irradiation, hypoxia and
The ‘closed-loop’ or ‘circular’ structure of mRNA
How 3′-UTR-binding proteins regulate the initiation of translation at the distant 5′ terminus is less obvious than how 5′-UTR-binding proteins regulate initiation. However, experiments in several different areas of mRNA biology have led investigators to arrive at a common conclusion: the ‘head’ and ‘tail’ of a transcript might be spatially proximate as a result of interactions between the ends 15, 16. An early indication of a functional interaction between transcript termini came from the
Circularization of mRNA: variations on a theme
The biological importance of 5′–3′ interactions of coding RNA is underscored by the diversity of mechanisms of transcript closure that have evolved in organisms ranging from viruses to humans. In the simplest example yet described, the positive-strand RNA genome of barley yellow dwarf virus (Fig. 2b) forms a closed loop in the absence of either a cap or a poly(A) tail, by direct base-pairing (‘kissing’) between a 105-nt translation element in the 3′-UTR and the 5′-UTR; an as-yet unidentified
Transcript circularization in translational control
Several mechanisms have been proposed for the regulation of initiation by transcript circularization. The observation that eIF4G mediates poly(A)-tail-dependent translation suggests that the eIF4G–PABP complex enhances ribosome recruitment, possibly by directed recycling of the 40S ribosomal subunit from the 3′-UTR to the 5′ terminus (Fig. 3a) [30]. In this case, disruption of the 5′–3′ interaction – by intercepting the interaction of PABP either with the poly(A) tail (Fig. 3bi) or with eIF4G (
Transcript 3′-UTRs: regions of opportunity and risk
Binding of the IRE-binding protein to the 5′-UTR IRE of ferritin and binding of hnRNP K and hnRNP E1 to the 3′-UTR DICE of 15-lipoxygenase are the prototypic, and perhaps best-understood, mechanisms of translational control by trans-acting factors. In the past six years, we have begun to appreciate the diversity of translational control mechanisms, many of them involving protein interactions at the 3′-UTR. At the same time, substantial biochemical, morphological and functional evidence has
Acknowledgements
Our work was supported by Public Health Service grants HL-29582 and HL-52692 from the National Heart Lung and Blood Institute, National Institutes of Health (to P.L.F.), and by a Scientist Development Grant from the American Heart Association, National Affiliate (to B.M.). We are grateful to Ken Kula for artistry.
References (53)
Gene-specific regulation by general translation factors
Cell
(2002)Regulating the fate of mRNA: the control of cellular iron metabolism
Cell
(1993)IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex eIF4F
Mol. Cell
(1998)- et al.
mRNA turnover
Curr. Opin. Cell Biol.
(2001) - et al.
A conserved AU sequence from the 3′ untranslated region of GM–CSF mRNA mediates selective mRNA degradation
Cell
(1986) A PUF family portrait: 3′UTR regulation as a way of life
Trends Genet.
(2002)A tale of two termini: a functional interaction between the termini of an mRNA is a prerequisite for efficient translation initiation
Gene
(1998)Life and death in the cytoplasm: messages from the 3′ end
Curr. Opin. Genet. Dev.
(1997)Circularization of mRNA by eukaryotic translation initiation factors
Mol. Cell
(1998)Base-pairing between untranslated regions facilitates translation of uncapped, nonpolyadenylated viral RNA
Mol. Cell
(2001)
Cap-poly(A) synergy in mammalian cell-free extracts. Investigation of the requirements for poly(A)-mediated stimulation of translation initiation
J. Biol. Chem.
Rotavirus protein NSP3 shuts off host cell protein synthesis
Virology
A mechanism for translationally coupled mRNA turnover: Interaction between the poly(A) tail and a c-fos RNA coding determinant via a protein complex
Cell
Maskin is a CPEB-associated factor that transiently interacts with elF-4E
Mol. Cell
mRNA silencing in erythroid differentiation: hnRNP K and hnRNP E1 regulate 15-lipoxygenase translation from the 3′ end
Cell
Lipoxygenase mRNA silencing in erythroid differentiation: the 3′UTR regulatory complex controls 60S ribosomal subunit joining
Cell
Human interferon-γ mRNA autoregulates its translation through a pseudoknot that activates the interferon-inducible protein kinase PKR
Cell
Hereditary hyperferritinemia-cataract syndrome caused by a 29-base pair deletion in the iron responsive element of ferritin L-subunit gene
Blood
Analysis of a Charcot–Marie–Tooth disease mutation reveals an essential internal ribosome entry site element in the connexin-32 gene
J. Biol. Chem.
Urokinase gene 3′-UTR T/C polymorphism is associated with urolithiasis
Urology
The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation
Dev. Biol.
Eukaryotic translation initiation: there are (at least) two sides to every story
Nat. Struct. Biol.
Molecular mechanisms of translation initiation in eukaryotes
Proc. Natl. Acad. Sci. U. S. A.
Upstream open reading frames as regulators of mRNA translation
Mol. Cell. Biol.
Internal ribosome entry sites in eukaryotic mRNA molecules
Genes Dev.
mRNA localization: message on the move
Nat. Rev. Mol. Cell Biol.
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