Complex splicing control of the human Thrombopoietin gene by intronic G runs
Open Access
- 7 December 2006
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 35 (1) , 132-142
- https://doi.org/10.1093/nar/gkl965
Abstract
The human thrombopoietin (THPO) gene displays a series of alternative splicing events that provide valuable models for studying splicing mechanisms. The THPO region spanning exon 1–4 presents both alternative splicing of exon 2 and partial intron 2 (IVS2) retention following the activation of a cryptic 3′ splice site 85 nt upstream of the authentic acceptor site. IVS2 is particularly rich in stretches of 3–5 guanosines (namely, G1–G10) and we have characterized the role of these elements in the processing of this intron. In vivo studies show that runs G7–G10 work in a combinatorial way to control the selection of the proper 3′ splice site. In particular, the G7 element behaves as the splicing hub of intron 2 and its interaction with hnRNP H1 is critical for the splicing process. Removal of hnRNP H1 by RNA interference promoted the usage of the cryptic 3′ splice site so providing functional evidence that this factor is involved in the selection of the authentic 3′ splice site of THPO IVS2.Keywords
This publication has 38 references indexed in Scilit:
- Role of Viral Splicing Elements and Cellular RNA Binding Proteins in Regulation of HIV-1 Alternative RNA SplicingCurrent HIV Research, 2006
- Splicing Error in E1α Pyruvate Dehydrogenase mRNA Caused by Novel Intronic Mutation Responsible for Lactic Acidosis and Mental RetardationJournal of Biological Chemistry, 2003
- Transcription of Different Exons 1 of the Human Neuronal Nitric Oxide Synthase Gene Is Dynamically Regulated in a Cell- and Stimulus- Specific MannerBiological Chemistry, 2003
- Regulation of 3′ Splice Site Selection in the 844ins68 Polymorphism of the Cystathionine β-Synthase GenePublished by Elsevier ,2002
- A Proinsulin Gene Splice Variant with Increased Translation Efficiency Is Expressed in Human Pancreatic IsletsEndocrinology, 2002
- Identification and characterization of a novel human cathepsin L splice variantGene, 2002
- hnRNP A1 controls HIV-1 mRNA splicing through cooperative binding to intron and exon splicing silencers in the context of a conserved secondary structureRNA, 2002
- Exon Identity Established through Differential Antagonism between Exonic Splicing Silencer-Bound hnRNP A1 and Enhancer-Bound SR ProteinsMolecular Cell, 2001
- Fragile X Mental Retardation Protein Targets G Quartet mRNAs Important for Neuronal FunctionPublished by Elsevier ,2001
- A Second Exon Splicing Silencer within Human Immunodeficiency Virus Type 1 tat Exon 2 Represses Splicing of Tat mRNA and Binds Protein hnRNP HJournal of Biological Chemistry, 2001