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  • Review Article
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The power of the 3′ UTR: translational control and development

Key Points

  • Many crucial decisions made during development are regulated by elements that are located in the 3′ untranslated region (3′ UTR) that control translation.

  • In several organisms, including Drosophila and Caenorhabditis elegans, cascades of translational regulators have central roles in tissue patterning and embryonic axis formation.

  • Many translational regulators are highly conserved and seem to control the activity of numerous mRNAs.

  • Translational regulation often involves the interaction of a given regulator with other factors, and depending on its partners will determine if it is an activator or repressor of translation.

  • Biochemical analysis of several translational control mechanisms indicates that there are many ways to regulate the translation of an mRNA. 3′-UTR binding factors control translation by regulating such diverse steps as ribosome binding, scanning, initiation and elongation.

  • The 'nuclear history' of an mRNA can also affect its translational activity. Several recent papers indicate that factors might be loading onto mRNAs in the nucleus, possibly during processing, that might later affect ribosome recruitment in the cytoplasm.

Abstract

Many crucial decisions, such as the location and timing of cell division, cell-fate determination, and embryonic axes establishment, are made in the early embryo, a time in development when there is often little or no transcription. For this reason, the control of variation in gene expression in the early embryo often relies on post-transcriptional control of maternal genes. Although the early embryo is rife with translational control, controlling mRNA activity is also important in other developmental processes, such as stem-cell proliferation, sex determination, neurogenesis and erythropoiesis.

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Figure 1: Embryonic axis determination in Drosophila.
Figure 2: Regulation of pal-1 and glp-1 mRNAs in C. elegans embryonic axis formation.
Figure 3: The mitosis/meiosis decision in the C. elegans germline.
Figure 4: The sperm–oocyte switch in C. elegans hermaphrodite germline.
Figure 5: A simplified view of eukaryotic translation initiation.
Figure 6: Mechanisms of translational control in developmental processes.

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Acknowledgements

We would like to thank members of the Goodwin laboratory, S. Crittenden, C. Eckmann, N. Hecht, P. Macdonald and F. Slack for discussion and criticial reading of the manuscript. We also thank T. Schedl for allowing us to discuss unpublished results. E.B.G. is supported by a grant from the National Institutes of Health.

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DATABASES

FlyBase

Apontic

Aubergine

bantam

bicoid

Brain tumor

Bruno

caudal

hid

hunchback

Maleless

MSL-2

nanos

Orb

oskar

p50

Pumilio

SXL

Staufen

Vasa

WormBase

GLD-1

GLD-2

GLD-3

glp-1

let-7

lin-4

MEX-3

MEX-5

MEX-6

pal-1

PAR-1

POS-1

SPN-4

tra-2

FURTHER INFORMATION

Elizabeth B. Goodwin's laboratory

Glossary

RNA INTERFERENCE

(RNAi). A process by which double-stranded RNA silences specifically the expression of homologous genes through degradation of their cognate mRNA.

BLASTOMERE

An early embryonic cell that is derived from the cleavage of a fertilized egg.

SPINDLE

An array of microtubules and associated molecules that forms between the opposite poles of a eukaryotic cell during cell division. It functions to move the duplicated chromosomes apart.

PACHYTENE

The third phase of prophase I in meiosis

DISTAL TIP CELL

A cell that is located adjacent to the distal end of the germline. It signals to the germline to maintain mitotic proliferation.

HELICASE

An enzyme that separates the two nucleic acid strands in a double helix, which results in the formation of regions of single-stranded DNA or RNA.

SPERMATID

A post-meiotic, haploid germ cell.

HETEROCHRONIC

heterochronic mutations alter the relative timing of developmental events as an organism grows (from the Greek heteros, meaning 'other' or 'different', and chronos, meaning 'time').

RETICULOCYTE

The youngest red blood cell normally found in the circulation, freshly released from the bone marrow (or other site of erythropoiesis).

DIOXYGENATION

The incorporation of both oxygen atoms of O2.

NONSENSE-MEDIATED DECAY

(NMD). A pathway ensuring that mRNAs that have premature stop codons are eliminated as templates for translation.

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Kuersten, S., Goodwin, E. The power of the 3′ UTR: translational control and development. Nat Rev Genet 4, 626–637 (2003). https://doi.org/10.1038/nrg1125

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