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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4391-4398.
Prepublished online as a Blood First Edition Paper on February 2, 2006; DOI 10.1182/blood-2005-12-4822.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
hnRNP L regulates differences in expression of mouse integrin 2 1
Yann Cheli, and
Thomas J. Kunicki
From the Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
There is a 2-fold variation in platelet integrin 2 1 levels among inbred mouse strains. Decreased 2 1 in 4 strains carrying Itga2 haplotype 2 results from decreased affinity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron 1. Seven strains bearing haplotype 1 and a 21 CA repeat sequence at this position (CA21) express twice the level of platelet 2 1 and exhibit an equivalent gain of platelet function in vitro. By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6. By cell-free, in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an increased proportion of alternatively spliced product. The splicing enhancer activity of CA21 in vivo is abolished by prior treatment with hnRNP Lspecific siRNA. Thus, decreased surface 2 1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1.

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