A multimegabase cluster of snRNA and tRNA genes on chromosome 1p36 harbours an adenovirus/SV40 hybrid virus integration site

Abstract

Adenovirus type 12 (Ad12) induces gaps at chromosomal bands 1p36, 1q21, 1q42–43 and 17q21 after infection of human embryonic kidney cells. Three of these bands harbour small nuclear RNA genes or pseudogenes, but the study of a possible relationship has been hampered by the lytic character of adenovirus infection. A non-lytic Ad5/SV40 hybrid virus preferentially integrates at 1p36 and the integration site has been cloned. Chromosomal band 1p36 encodes genes for small nuclear RNA U1 (RNU–1) and for the tRNAs of glutamlc acid (TRE) and asparaglne (TRN). Each of these genes Is encoded by 15–30 copies. We studied the organization of these genes and of the viral integration site by pulsed field gel electrophoresis (PFGE) and analysis of yeast artificial chromosomes (YACs). We show that RNU–1, TRE and TRN genes are scattered over a region of probably more than 2 Mb with intergenic distances of up to 125 kb. The Ad5/SV40 Integration site maps to Identical chromosomal Notl fragments as RNU–1 and TRE. Fine mapping of a YAC shows that the integration site is within 40–70 kb of genes for RNU–1, TRN and TRE.