Nucleic Acids Research Advance Access originally published online on December 7, 2006
Nucleic Acids Research 2007 35(1):132-142; doi:10.1093/nar/gkl965
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Nucleic Acids Research, 2007, Vol. 35, No. 1 132-142
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Complex splicing control of the human Thrombopoietin gene by intronic G runs
1 International Centre for Genetic Engineering and Biotechnology, Padriciano 99 I-34012, Trieste, Italy 2 Department of Physiology and Pathology, University of Trieste Via A. Fleming 22, 34127, Trieste, Italy
*To whom correspondence should be addressed. Tel: +39 040 375 7337; Fax: +39 040 375 7361; Email: baralle{at}icgeb.org
Received August 7, 2006. Revised September 28, 2006. Accepted October 17, 2006.
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.
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