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Differential Subcellular Distributions and Trafficking Functions of hnRNP A2/B1 Spliceoforms
- Source :
- Traffic. 11:886-898
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Trafficking of mRNA molecules from the nucleus to distal processes in neural cells is mediated by heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 trans-acting factors. Although hnRNP A2/B1 is alternatively spliced to generate four isoforms, most functional studies have not distinguished between these isoforms. Here, we show, using isoform-specific antibodies and isoform-specific green fluorescent protein (GFP)-fusion expression constructs, that A2b is the predominant cytoplasmic isoform in neural cells, suggesting that it may play a key role in mRNA trafficking. The differential subcellular distribution patterns of the individual isoforms are determined by the presence or absence of alternative exons that also affect their dynamic behavior in different cellular compartments, as measured by fluorescence correlation spectroscopy. Expression of A2b is also differentially regulated with age, species and cellular development. Furthermore, coinjection of isoform-specific antibodies and labeled RNA into live oligodendrocytes shows that the assembly of RNA granules is impaired by blockade of A2b function. These findings suggest that neural cells modulate mRNA trafficking by regulating alternative splicing of hnRNP A2/B1 and controlling expression levels of A2b, which may be the predominant mediator of cytoplasmic-trafficking functions. These findings highlight the importance of considering isoform-specific functions for alternatively spliced proteins.
- Subjects :
- Gene isoform
Cytoplasm
Heterogeneous nuclear ribonucleoprotein
Recombinant Fusion Proteins
Green Fluorescent Proteins
RNA-binding protein
Biology
Cytoplasmic Granules
Heterogeneous ribonucleoprotein particle
Hippocampus
Biochemistry
Heterogeneous-Nuclear Ribonucleoproteins
Article
Neuroblastoma
Structural Biology
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Genetics
medicine
Animals
Humans
Protein Isoforms
RNA, Messenger
Molecular Biology
Cells, Cultured
Cell Nucleus
Neurons
Messenger RNA
Alternative splicing
RNA
Exons
Cell Biology
Rats
Cell biology
Alternative Splicing
Oligodendroglia
Protein Transport
Cell nucleus
medicine.anatomical_structure
Trans-Activators
HeLa Cells
Subcellular Fractions
Subjects
Details
- ISSN :
- 13989219
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Traffic
- Accession number :
- edsair.doi.dedup.....cb723e43dd27046a526ff8ad00ae910d