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mRNA localization: message on the move

Key Points

  • An essential part of spatial control of gene expression is cytoplasmic messenger RNA localization. Several putative functions for mRNA localization have been proposed. They include efficient control of local protein synthesis and facilitation of co-translational complex assembly. A new function might be the support of protein targeting to specific organelles.

  • mRNA localization can be achieved by local transcript protection, directed transport along cytoskeletal filaments and cytoplasmic streaming (facilitated diffusion).

  • A general model for localization by active transport involves mRNA recognition (probably inside the nucleus), association of a core ribonucleoprotein (RNP) complex with cytoskeletal motor proteins and tethering of the delivered RNA at the destination site.

  • mRNA localization requires specific cis-acting signals ('zi p codes') that are generally found in the 3′ UTR. Recent examples however indicate that zip codes can also be located in the 5′ UTR or the coding region.

  • Zip codes can be short defined nucleotide stretches, simple secondary structures ('stem loops') or highly structured regions with multiple sequentially acting or repetitive signals.

  • Zip-code-binding proteins recognize a specific mRNA structure and/or a specific sequence within their cognate target. Some zip-code-binding proteins belong to the hnRNP protein family and can shuttle between nucleus and cytoplasm. They might associate with localized mRNAs inside the nucleus, implying that they accompany the cognate mRNA to the cytoplasm. Shuttling hnRNP proteins might serve as a 'tag' to mark mRNAs that have to be localized.

  • Cytoplasmic mRNA transport occurs in the form of large RNP complexes ('mRNA granules'). It is not yet clear how mRNA granules are generated and what they are constructed of. Biochemical purification of RNP transport complexes has recently been initiated. Analysis of yeast and Drosophila RNPs will provide us with a first idea of the function of protein components of localized RNPs.

Abstract

Cytoplasmic messenger RNA localization is a key post-transcriptional mechanism of establishing spatially restricted protein synthesis. The characterization of cis-acting signals within localized mRNAs, and the identification of trans-acting factors that recognize these signals, has opened avenues towards identifying the machinery and mechanisms involved in mRNA transport and localization.

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Figure 1: Examples of localized mRNAs and zip-code-binding proteins.
Figure 2: Model for mRNA transport.
Figure 3: Modular structure of zip-code-binding proteins.
Figure 4: Types of mRNA zip codes.

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Acknowledgements

I apologize to all colleagues whose work has not been properly discussed owing to limited space. I am grateful to J. Carson, R. Cohen, A. Ephrussi, J. Hesketh, M. Kiebler, S. Kindler, R. Long, B. Schnapp and R. Singer for providing Figures and movies. I would like to thank especially A. Ephrussi, M. Kiebler, A. Jaedicke and three further colleagues for encouraging comments and suggestions, and members of my lab for their contribution to numerous discussions on the subject.

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DATABASE LINKS

ASH1

bicoid

nanos

oskar

Atm1

Ist2

Staufen

Gurken

prospero

Myo4

Squid

Fushi-tarazu

FURTHER INFORMATION

movie of Ash1

movie of mStaufen

St Johnston lab

Ephrussi lab

Mowry lab

Lipshitz lab

Kiebler lab

ENCYCLOPEDIA OF LIFE SCIENCES

RNA intracellular transport

Glossary

ABC TRANSPORTER

Member of a membrane-spanning transporter protein family containing an ATP-binding cassette (ABC).

3′ UNTRANSLATED REGION

Non-coding region that lies 3′ to the protein-coding part of a messenger RNA; often contains sequences involved in mRNA regulation.

STEM LOOP

Messenger RNA secondary structure containing a single-stranded loop region between the base-paired helical stem.

NURSE CELL

Auxiliary cell that supplies the oocyte with synthesized messenger RNAs and proteins during insect oogenesis.

GERM PLASM

A special cytoplasmic region in (dividing) eggs that contains primary germ-cell-determining factors.

MYELIN

Proteins produced by Schwann cells or oligodendrocytes that cause adjacent plasma membranes to stack tightly together.

OLIGODENDROCYTE

Glial cell type in the central nervous system with myelin-containing processes that wrap around axons and help to facilitate conduction of electrical signals.

5′ UNTRANSLATED REGION

Non-coding region that lies 5′ to the protein-coding part of a messenger RNA.

PERIKARYON

Cell body of neurons or glial cells, containing the nucleus and most organelles.

TYPE V MYOSIN

Subclass of the myosin protein family of actin-dependent motor proteins, required for transport of vesicles or messenger RNA cargo.

NUCLEAR-EXPORT SIGNAL

Amino-acid sequence required for active transport of certain proteins from the nucleus to the cytoplasm.

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Jansen, RP. mRNA localization: message on the move. Nat Rev Mol Cell Biol 2, 247–256 (2001). https://doi.org/10.1038/35067016

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