Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame.

Abstract

The His-i locus is a common site of viral insertion in murine myeloid leukemias induced by the wild mouse ecotropic retrovirus, CasBrM. In this report, we describe the cloning of a novel gene at the His-i locus and show that His-i expression is associated with the transformed phenotype. Northern (RNA) blot analysis identified His-i transcripts in four transformed myeloid cell lines but in no normal tissues examined. Two of these cell lines were derived from retrovirus-induced myeloid leukemias that harbor integrated proviruses which drive His-i gene expression by promoter insertion. The two other cell lines expressed a discrete 3-kb His-i RNA that is derived from a novel gene consisting of three exons that span 6 kb on mouse chromosome 2. The His-i gene is conserved as a single-copy sequence in multiple vertebrate species and is expressed as a spliced and polyadenylated RNA. A protein-coding region is not evident from analysis of the His-i sequence because of the presence of multiple small open reading frames, none of which are greater than 219 bp. This lack of an extensive open reading frame is an unusual feature that is shared by other RNA molecules believed to function in the absence of translation.

A novel synapse-associated noncoding RNA.

“…The 7H4 gene differs from H19 and XIST in that it has no introns and its expression is highly tissue specific. Recently, another noncoding RNA, expressed at the His-i locus, has been cloned from transformed mouse cell lines, although it is unclear if this RNA is expressed in vivo (2).…”

Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients

“…H19 appears to be lost in certain embryonal tumors (Hao et al, 1993), but overexpressed in a small subset of breast cancers (Lottin et al, 2002). Retroviral insertion events appear to activate the expression of Bic (Tam et al, 1997) and of His-1 (Askew et al, 1994), but cancer-associated expression of these genes in humans has not been reported. The expanding universe of noncoding RNAs and their functional evaluations may define additional genes with potential functions in the process of tumorigenesis.…”

“…Recent results, however, indicated that in breast epithelial cells, H19 overexpression promotes tumor progression without affecting cell proliferation (Lottin et al, 2002). His-1 (Askew et al, 1994) and Bic (Tam et al, 1997) are noncoding RNA genes whose transcription is activated by retroviral insertion, and they are implicated in the pathogenesis of hematological malignancies. Avian bic cooperates with c-myc in oncogenesis, and in enhancing the growth of chicken embryo fibroblasts (Tam et al, 2002).…”

Disruption of a novel gene, DIRC3, and expression of DIRC3‐HSPBAP1 fusion transcripts in a case of familial renal cell cancer and t(2;3)(q35;q21)

“…An extensive open reading frame could not be predicted and we conclude that the gene product may act as a noncoding RNA. Other genes known to express noncoding RNAs include H19, XIST, His-1, Bic, BORG, SRA, and DD3 (Brannan et al, 1990;Brockhoff et al, 1992;Hao et al, 1993;Askew et al, 1994;Velleca et al, 1994;Takeda et al, 1998;Tam et al, 1998;Bussemakers et al, 1999;Lanz et al, 1999). Some of these genes have been implicated in tumor development.…”