Trends in Plant Science
Volume 9, Issue 4, April 2004, Pages 174-179
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Regulation of senescence by eukaryotic translation initiation factor 5A: implications for plant growth and development

https://doi.org/10.1016/j.tplants.2004.02.008Get rights and content

Abstract

Regulation of protein synthesis is increasingly being recognized as an important determinant of cell proliferation and senescence. In particular, recent evidence indicates that eukaryotic translation initiation factor 5A (eIF-A) plays a pivotal role in this determination. Separate isoforms of eIF-5A appear to facilitate the translation of mRNAs required for cell division and cell death. This raises the possibility that eIF-5A isoforms are elements of a biological switch that is in one position in dividing cells and in another position in dying cells. Changes in the position of this putative switch in response to physiological and environmental cues are likely to have a significant impact on plant growth and development.

Section snippets

eIF-5A is post-translationally activated

Genes encoding eIF-5A are thought to be present in all eukaryotic cells [10]. Earlier studies with yeast and mammalian cells demonstrated that eIF-5A is synthesized as an inactive protein and post-translationally activated through the sequential actions of two enzymes, deoxyhypusine synthase (DHS) (EC 2.5.1.46) and deoxyhypusine hydroxylase (DHH) (EC 1.14.99.29) 11, 12. DHS mediates the addition of butylamine derived from spermidine to the ϵ amino group of a highly conserved lysine in the

eIF-5A is not a conventional translation initiation factor

Hypusine-modified eIF-5A was originally isolated from immature red blood cells and was identified as a translation initiation factor based on its ability to stimulate the formation of methionyl-puromycin, a dipeptide analog, under in vitro conditions [19]. However, this proposed function for eIF-5A has since been questioned because a similar effect on translation is not observed in situ 20, 21. Moreover, eIF-5A appears not to be required for global protein synthesis. For example, only marginal

Multiple isoforms of eIF-5A and their possible functions

One of the first indications that eIF-5A selectively facilitates translation came from studies with yeast. Mutating the single isoform of DHS, which depleted the cells of activated eIF-5A, resulted in only marginal changes in total protein synthesis 11, 12, 22. Moreover, the DHS mutants proved to be incapable of cell division, yet remained alive and enlarged. Inactivation of both isoforms of eIF-5A in yeast produced the same phenotype 33, 34. A correlation between growth arrest and a reduction

Pleiotropic effects of suppressing eIF-5A activation

Reducing endogenous DHS protein and, accordingly, levels of activated eIF-5A in Arabidopsis by constitutively expressing an antisense DHS transgene has been shown to have dramatic effects on growth and development [15]. Among these is a delay in rosette leaf senescence ranging from 2 weeks to >6 weeks depending on the degree of DHS suppression. Moreover, transgenic plants with the greatest delay in leaf senescence (>6 weeks) also exhibited delayed bolting, implying, as had been suggested

Interplay between eIF-5A isoforms – are they elements of a death switch?

In plants, there appear to be at least three isoforms of eIF-5A, one possibly regulating cell division and two or more possibly regulating senescence. The likelihood that eIF-5A selectively shuttles mRNAs across the nuclear envelope raises the possibility that its isoforms could be elements of a biological switch controlling the onset of programmed cell death.

How might this switch work? Expression analyses of eIF-5A in Arabidopsis have indicated that the isoforms of eIF-5A are expressed

Acknowledgments

We are grateful for helpful discussions with Yulia Gatsukovich during the preparation of this manuscript. We are also grateful for a grant-in-aid of research from the Natural Sciences and Engineering Research Council of Canada.

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