HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 32, 23553-23560, August 10, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/32/23553    most recent M702045200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Feng, Y. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Feng, Y. Social Bookmarking                      What's this?

The Selective RNA-binding Protein Quaking I (QKI) Is Necessary and Sufficient for Promoting Oligodendroglia Differentiation^*

Yuntao Chen, Donghua Tian, Li Ku, Donna J. Osterhout, and Yue Feng¹

From the Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322 and the Department of Cell and Developmental Biology SUNY Upstate Medical University, Syracuse, New York 13210

Quaking I (QKI) is a selective RNA-binding protein essential for myelination of the central nervous system. Three QKI isoforms with distinct C termini and subcellular localization, namely QKI-5, QKI-6, and QKI-7, are expressed in oligodendroglia progenitor cells (OPCs) prior to the initiation of myelin formation and implicated in promoting oligodendrocyte lineage development. However, the functional requirement for each QKI isoform and the mechanisms by which QKI isoforms govern OPC development still remain elusive. We report here that exogenous expression of each QKI isoform is sufficient to enhance differentiation of OPCs with different efficiency, which is abolished by a point mutation that abrogates the RNA binding activity of QKI. Reciprocally, small interfering RNA-mediated QKI knockdown blocks OPC differentiation, which can be partly rescued by QKI-5 and QKI-6 but not by QKI-7, indicating the differential requirement of QKI isoform function in advancing OPC differentiation. Furthermore, we found that abrogation of OPC differentiation, as a result of QKI deficiency, is not due to altered proliferation capacity or cell cycle progression. These results indicate that QKI isoforms are necessary and sufficient for promoting OPC development, which must involve direct influence of QKI on differentiation/maturation of OPCs independent of cell cycle exit, likely via regulating the expression of the target mRNAs of QKI that support OPC differentiation.

Received for publication, March 8, 2007 , and in revised form, June 6, 2007.

^* This work is supported by National Institutes of Health Grants NS39551 and NS056097, and National Multiple Sclerosis Society Grant RG 3296. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Pharmacology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322. Tel.: 404-727-0351; Fax: 404-727-0365; E-mail: yfeng{at}emory.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?