| First Author | Cheli Y | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 11 | Pages | 4391-8 |
| PubMed ID | 16455949 | Mgi Jnum | J:132872 |
| Mgi Id | MGI:3777070 | Doi | 10.1182/blood-2005-12-4822 |
| Citation | Cheli Y, et al. (2006) hnRNP L regulates differences in expression of mouse integrin alpha2beta1. Blood 107(11):4391-8 |
| abstractText | There is a 2-fold variation in platelet integrin alpha2beta1 levels among inbred mouse strains. Decreased alpha2beta1 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 alpha2beta1 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 L-specific siRNA. Thus, decreased surface alpha2beta1 results from decreased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific site in intron 1. |
