Journalartikel

Jahr der Veröffentlichung: 2009

Seiten: 1442-1451

Zeitschrift: Molecular and Cellular Biology

Bandnummer: 29

Heftnummer: 6

ISSN: 0270-7306

eISSN: 1098-5549

Open Access Status: Green

DOI Link: https://doi.org/10.1128/MCB.01689-08

Verlag: Taylor and Francis Group

Abstract: 
We recently characterized human hnRNP L as a global regulator of alternative splicing, binding to CA-repeat and CA-rich elements. Here we report that hnRNP L autoregulates its own expression on the level of alternative splicing. Intron 6 of the human hnRNP L gene contains a short exon that, if used, introduces a premature termination codon, resulting in nonsense-mediated decay (NMD). This "poison exon" is preceded by a highly conserved CA-rich cluster extending over 800 nucleotides that binds hnRNP L and functions as an unusually extended, intronic enhancer, promoting inclusion of the poison exon. As a result, excess hnRNP L activates NMD of its own mRNA, thereby creating a negative autoregulatory feedback loop and contributing to homeostasis of hnRNP L levels. We present experimental evidence for this mechanism, based on NMD inactivation, hnRNP L binding assays, and hnRNP L-dependent alternative splicing of heterologous constructs. In addition, we demonstrate that hnRNP L cross-regulates inclusion of an analogous poison exon in the hnRNP L-like pre-mRNA, which explains the reciprocal expression of the two closely related hnRNP L proteins.

Harvard-Zitierstil: Rossbach, O., Hung, L., Schreiner, S., Grishina, I., Heiner, M., Hui, J., et al. (2009) Auto- and Cross-Regulation of the hnRNP L Proteins by Alternative Splicing, Molecular and Cellular Biology, 29(6), pp. 1442-1451. https://doi.org/10.1128/MCB.01689-08

APA-Zitierstil: Rossbach, O., Hung, L., Schreiner, S., Grishina, I., Heiner, M., Hui, J., & Bindereif, A. (2009). Auto- and Cross-Regulation of the hnRNP L Proteins by Alternative Splicing. Molecular and Cellular Biology. 29(6), 1442-1451. https://doi.org/10.1128/MCB.01689-08