RNA Protein Interaction in Neurons

Overview

Journal Annu Rev Neurosci

Specialty Neurology

Date 2013 May 25

PMID 23701460

Citations 101

Authors

Robert B Darnell

Affiliations

Soon will be listed here.

Abstract

Neurons have their own systems for regulating RNA. Several multigene families encode RNA binding proteins (RNABPs) that are uniquely expressed in neurons, including the well-known neuron-specific markers ELAV and NeuN and the disease antigen NOVA. New technologies have emerged in recent years to assess the function of these proteins in vivo, and the answers are yielding insights into how and why neurons may regulate RNA in special ways-to increase cellular complexity, to localize messenger RNA (mRNA) spatially, and to regulate their expression in response to synaptic stimuli. The functions of such restricted neuronal proteins are likely to be complemented by more widely expressed RNABPs that may themselves have developed specialized functions in neurons, including Argonaute/microRNAs (miRNAs). Here we review what is known about such RNABPs and explore the potential biologic and neurologic significance of neuronal RNA regulatory systems.

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References

Darnell R, DeAngelis L . Regression of small-cell lung carcinoma in patients with paraneoplastic neuronal antibodies. Lancet. 1993; 341(8836):21-2. DOI: 10.1016/0140-6736(93)92485-c. View

Da Cruz S, Cleveland D . Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr Opin Neurobiol. 2011; 21(6):904-19. PMC: 3228892. DOI: 10.1016/j.conb.2011.05.029. View

Fan X, Steitz J . Overexpression of HuR, a nuclear-cytoplasmic shuttling protein, increases the in vivo stability of ARE-containing mRNAs. EMBO J. 1998; 17(12):3448-60. PMC: 1170681. DOI: 10.1093/emboj/17.12.3448. View

Ming G, Wong S, Henley J, Yuan X, Song H, Spitzer N . Adaptation in the chemotactic guidance of nerve growth cones. Nature. 2002; 417(6887):411-8. DOI: 10.1038/nature745. View

Okabe M, Imai T, Kurusu M, Hiromi Y, Okano H . Translational repression determines a neuronal potential in Drosophila asymmetric cell division. Nature. 2001; 411(6833):94-8. DOI: 10.1038/35075094. View

Yang Y, Yin G, Darnell R . The neuronal RNA-binding protein Nova-2 is implicated as the autoantigen targeted in POMA patients with dementia. Proc Natl Acad Sci U S A. 1998; 95(22):13254-9. PMC: 23773. DOI: 10.1073/pnas.95.22.13254. View

Gao F, Carson C, Levine T, Keene J . Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1. Proc Natl Acad Sci U S A. 1994; 91(23):11207-11. PMC: 45196. DOI: 10.1073/pnas.91.23.11207. View

Szabo A, Dalmau J, Manley G, Rosenfeld M, Wong E, Henson J . HuD, a paraneoplastic encephalomyelitis antigen, contains RNA-binding domains and is homologous to Elav and Sex-lethal. Cell. 1991; 67(2):325-33. DOI: 10.1016/0092-8674(91)90184-z. View

Zhang C, Zhang Z, Castle J, Sun S, Johnson J, Krainer A . Defining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2. Genes Dev. 2008; 22(18):2550-63. PMC: 2546699. DOI: 10.1101/gad.1703108. View

10.

Kuroyanagi H . Fox-1 family of RNA-binding proteins. Cell Mol Life Sci. 2009; 66(24):3895-907. PMC: 2777236. DOI: 10.1007/s00018-009-0120-5. View

11.

Jain R, Andrews L, McGowan K, Pekala P, Keene J . Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes. Mol Cell Biol. 1997; 17(2):954-62. PMC: 231821. DOI: 10.1128/MCB.17.2.954. View

12.

Ruggiu M, Herbst R, Kim N, Jevsek M, Fak J, Mann M . Rescuing Z+ agrin splicing in Nova null mice restores synapse formation and unmasks a physiologic defect in motor neuron firing. Proc Natl Acad Sci U S A. 2009; 106(9):3513-8. PMC: 2642475. DOI: 10.1073/pnas.0813112106. View

13.

Lee J, Tang Z, Black D . An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of downstream neuronal target exons. Genes Dev. 2009; 23(19):2284-93. PMC: 2758739. DOI: 10.1101/gad.1837009. View

14.

Sutton M, Wall N, Aakalu G, Schuman E . Regulation of dendritic protein synthesis by miniature synaptic events. Science. 2004; 304(5679):1979-83. DOI: 10.1126/science.1096202. View

15.

Huttelmaier S, Zenklusen D, Lederer M, Dictenberg J, Lorenz M, Meng X . Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1. Nature. 2005; 438(7067):512-5. DOI: 10.1038/nature04115. View

16.

Robinow S, Campos A, Yao K, White K . The elav gene product of Drosophila, required in neurons, has three RNP consensus motifs. Science. 1988; 242(4885):1570-2. DOI: 10.1126/science.3144044. View

17.

Liu N, Landreh M, Cao K, Abe M, Hendriks G, Kennerdell J . The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature. 2012; 482(7386):519-23. PMC: 3326599. DOI: 10.1038/nature10810. View

18.

Sharma S, Maris C, Allain F, Black D . U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression. Mol Cell. 2011; 41(5):579-88. PMC: 3931528. DOI: 10.1016/j.molcel.2011.02.012. View

19.

Polydorides A, Okano H, Yang Y, Stefani G, Darnell R . A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc Natl Acad Sci U S A. 2000; 97(12):6350-5. PMC: 18606. DOI: 10.1073/pnas.110128397. View

20.

Jensen K, Dredge B, Stefani G, Zhong R, Buckanovich R, Okano H . Nova-1 regulates neuron-specific alternative splicing and is essential for neuronal viability. Neuron. 2000; 25(2):359-71. DOI: 10.1016/s0896-6273(00)80900-9. View