mRNA localization: an orchestration of assembly, traffic and synthesis - PubMed (original) (raw)

Review

mRNA localization: an orchestration of assembly, traffic and synthesis

Lei Xing et al. Traffic. 2013 Jan.

Abstract

Asymmetrical mRNA localization and subsequent local translation provide efficient mechanisms for protein sorting in polarized cells. Defects in mRNA localization have been linked to developmental abnormalities and neurological diseases. Thus, it is critical to understand the machineries mediating and mechanisms underlying the asymmetrical distribution of mRNA and its regulation. The goal of this review is to summarize recent advances in the understanding of mRNA transport and localization, including the assembly and sorting of transport messenger ribonucleic protein (mRNP) granules, molecular mechanisms of active mRNP transport, cytoskeletal interactions and regulation of these events by extracellular signals.

© 2012 John Wiley & Sons A/S.

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Figures

Figure 1

Figure 1. mRNA-binding proteins couple mRNAs to molecular motors for active transport

A, Yeast mRNA-binding protein She2p in a complex with She3p recruits myosin (Myo4/She1p) onto Ash1 mRNA. B, Drosophila non-canonical RNA-binding protein, Egl1, and Bic-D interact with dynein and dynactin complexes, respectively, to couple _TLS_-containing mRNAs to dynein for microtubule minus-end directed mRNA transport. C, FMRP facilitates the localization of its target mRNAs to dendritic compartments in mammalian neurons in response gp1 mGluR activation. FMRP may directly (left) or indirectly (right) interact with kinesin light chain (KLC) to couple mRNAs to conventional kinesin motors for mRNA localization.

Figure 2

Figure 2. A schematic view of the multistep process for mRNA localization

Mechanistic studies in different model systems reveal that mRNA localization is a multi-step process involving the assembly of mRNP granules, engagement of transport molecular motors and subsequent active transport and anchorage of mRNPs at the destination. (1) Assembly of transport mRNP granules can initiate from the nucleus, coupled to transcription and splicing. The binding of mRNA-binding proteins to nascent pre-mRNAs may help to maintain mature mRNAs in a translational quiescent state. EJCs are loaded onto mature mRNAs following the incision of introns. (2) mRNPs are exported into the cytoplasm. (3) mRNA-binding proteins interacting with zipcode elements recruit transport machineries by direct or indirect interaction with molecular motors including myosin, kinesin and dynein/dynactin complexes for microfilament or microtubule-mediated cargo transport. (4) Molecular motors couple mRNPs to microfilaments or microtubules for active transport. Molecular motor-mediated mRNA transport and localization requires intact cytoskeletal structures. (5) mRNPs are anchored to their destination. (6) Properly targeted and repressed mRNAs are released for local translation in response to local signaling events.

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