BIC, A NOVEL GENE ACTIVATED BY PROVIRAL INSERTIONS IN AVIAN-LEUKOSIS VIRUS-INDUCED LYMPHOMAS, IS LIKELY TO FUNCTION THROUGH ITS NONCODING RNA

The bic locus is a common retroviral integration site in avian leukosi s virus (ALV)-induced B-cell lymphomas originally identified by infect ion of chickens with ALVs of two different subgroups(Clurman and Haywa rd, Mel. Cell, Biol, 9:2657-2664, 1989), Based on its frequent associa tion with c-myc activation and its preferential activation in metastat ic tumors, the bic locus is thought to harbor a gene that can collabor ate with c-myc in lymphomagenesis and presumably plays a role in late stages of tumor progression. In the present study, we have cloned and characterized two novel genes, bdw and bic, at the bic locus. bdw enco ded a putative novel protein of 345 amino acids, However, its expressi on did not appear to be altered in tumor tissues, suggesting that it i s not involved in oncogenesis, The bic gene consisted of two exons and was expressed as two spliced and alternatively polyadenylated transcr ipts at low levels in lymphoid/hematopoietic tissues. In tumors harbor ing bic integrations, proviruses drove bic gene expression by promoter insertion, resulting in high levels of expression of a chimeric RNA c ontaining bic exon 2. Interestingly, bic lacked an extensive open read ing frame, implying that it may function through its RNA. Computer ana lysis of RNA from small exon 2 of bic predicted extensive double-stran ded structures, including a highly ordered RNA duplex between nucleoti des 316 and 461, The possible role of bic in cell growth and different iation is discussed in view of the emerging evidence that untranslated RNAs play a role in growth control.