title: Complex splicing control of the human Thrombopoietin gene by intronic G runs.
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.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Padriciano 99 I-34012, Trieste, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Marcucci
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Baralle
authors.forename: Maurizio
authors.initials: M
authors.lastname: Romano
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005091:Exons; D006151:Guanosine / Q000032:analysis*; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D034622:RNA Interference; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000737:chemistry; D013926:Thrombopoietin / Q000235:genetics* / Q000378:metabolism
chemical_list: D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D022821:RNA Splice Sites; D012333:RNA, Messenger; D006151:Guanosine; D013926:Thrombopoietin