Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms

Han, Siew Ping, Friend, Lexie R., Carson, John H., Korza, George, Barbarese, Elisa, Maggipinto, Michael, Hatfield, Jodie T., Rothnagel, Joseph A. and Smith, Ross (2010) Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms. Traffic, 11 7: 886-898. doi:10.1111/j.1600-0854.2010.01072.x

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Author Han, Siew Ping
Friend, Lexie R.
Carson, John H.
Korza, George
Barbarese, Elisa
Maggipinto, Michael
Hatfield, Jodie T.
Rothnagel, Joseph A.
Smith, Ross
Title Differential subcellular distributions and trafficking functions of hnRNP A2/B1 spliceoforms
Journal name Traffic   Check publisher's open access policy
ISSN 1398-9219
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1111/j.1600-0854.2010.01072.x
Volume 11
Issue 7
Start page 886
End page 898
Total pages 13
Editor Mark C. P. Marsh
Gerrit van Meer
Trina A. Schroer
Tom H. Stevens
Place of publication København, Denmark
Publisher Munksgaard
Collection year 2011
Language eng
Formatted 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.
© 2010 John Wiley & Sons A/S
Keyword Alternative splicing
hnRNP A2
mRNA trafficking
Subcellular distribution
Nuclear ribonucleoprotein A2
Response element
Intracellular trafficking
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
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Created: Sun, 27 Jun 2010, 00:00:32 EST