Journalartikel

Jahr der Veröffentlichung: 2012

Seiten: 5666-5678

Zeitschrift: Nucleic Acids Research

Bandnummer: 40

Heftnummer: 12

ISSN: 0305-1048

eISSN: 1362-4962

Open Access Status: Gold

DOI Link: https://doi.org/10.1093/nar/gks221

Verlag: Oxford University Press

Abstract: 
CD45 encodes a trans-membrane protein-tyrosine phosphatase expressed in diverse cells of the immune system. By combinatorial use of three variable exons 4-6, isoforms are generated that differ in their extracellular domain, thereby modulating phosphatase activity and immune response. Alternative splicing of these CD45 exons involves two heterogeneous ribonucleoproteins, hnRNP L and its cell-type specific paralog hnRNP L-like (LL). To address the complex combinatorial splicing of exons 4-6, we investigated hnRNP L/LL protein expression in human B-cells in relation to CD45 splicing patterns, applying RNA-Seq. In addition, mutational and RNA-binding analyses were carried out in HeLa cells. We conclude that hnRNP LL functions as the major CD45 splicing repressor, with two CA elements in exon 6 as its primary target. In exon 4, one element is targeted by both hnRNP L and LL. In contrast, exon 5 was never repressed on its own and only co-regulated with exons 4 and 6. Stable L/LL interaction requires CD45 RNA, specifically exons 4 and 6. We propose a novel model of combinatorial alternative splicing: HnRNP L and LL cooperate on the CD45 pre-mRNA, bridging exons 4 and 6 and looping out exon 5, thereby achieving full repression of the three variable exons.

Harvard-Zitierstil: Preußner, M., Schreiner, S., Hung, L., Porstner, M., Jäck, H., Benes, V., et al. (2012) HnRNP L and L-like cooperate in multiple-exon regulation of CD45 alternative splicing, Nucleic Acids Research, 40(12), pp. 5666-5678. https://doi.org/10.1093/nar/gks221

APA-Zitierstil: Preußner, M., Schreiner, S., Hung, L., Porstner, M., Jäck, H., Benes, V., Rätsch, G., & Bindereif, A. (2012). HnRNP L and L-like cooperate in multiple-exon regulation of CD45 alternative splicing. Nucleic Acids Research. 40(12), 5666-5678. https://doi.org/10.1093/nar/gks221