Disease relevance of RNU2

• Adenovirus type 12-induced fragility of the human RNU2 locus requires p53 function [1].
• We reported previously that the tandemly arrayed genes encoding U2 snRNA (the RNU2 locus) in humans and apes contain a solo LTR (U2-LTR) which was presumably generated by homologous recombination between the two LTRs of an ancestral provirus that is retained in the orthologous baboon RNU2 locus [2].
• Interestingly, the RNU2 locus in human fibrosarcoma line HT1080 is hypomethylated, and de novo methylation did not occur in an artificial U2 tandem array introduced by stable transfection [3].

High impact information on RNU2

• Concerted evolution of the tandemly repeated genes encoding human U2 snRNA (the RNU2 locus) involves rapid intrachromosomal homogenization and rare interchromosomal gene conversion [4].
• Using chromosome painting and the NGFR gene as an outside marker, we show that the U2 tandem array (RNU2) has remained at the same chromosomal locus (equivalent to human 17q21) through multiple speciation events over > 35 million years leading to the Old World monkey and hominoid lineages [5].
• Evidence for effective suppression of recombination in the chromosome 17q21 segment spanning RNU2-BRCA1 [6].
• Adenovirus type 12-induced fragility of the human RNU2 locus requires U2 small nuclear RNA transcriptional regulatory elements [7].
• YAC and cosmid clones were isolated and used to refine the location of this gene adjacent and proximal to the RNU2 locus [8].

Biological context of RNU2

• Characterization of associations between polymorphic sites located throughout the approximately 200-400-kb variable-length region spanning RNU2-BRCA1 reveals nearly complete linkage disequilibrium [6].
• Ad12-induced fragility of the RNU2 locus requires U2 snRNA transcriptional regulatory elements and viral early functions but not viral replication or integration, or chromosomal sequences flanking the RNU2 locus [1].
• The multigene family encoding human U2 small nuclear RNA (snRNA) is organized as a single large tandem array containing 5 to 25 copies of a 6.1-kb repeat unit (the RNU2 locus) [9].
• Infection of human cells with adenovirus 12 (Ad12), but not Ad2 or 5, induces four specific sites of metaphase chromosome fragility: the U1 small nuclear RNA (snRNA) genes (the RNU1 locus), the U2 snRNA genes (RNU2), the U1 snRNA pseudogenes (PSU1) and the 5S rRNA genes (RN5S) [10].
• We further show that the RNU2 loci of other catarrhine primates (gorilla, chimpanzee, orangutan, and baboon) contain orthologous CT microsatellites; these also exhibit length polymorphism, but are highly divergent from each other [11].

Associations of RNU2 with chemical compounds

• In the present study we have investigated the response of the RNU2 locus to cytosine arabinoside (araC), an inhibitor of DNA polymerases and a common inducer of fragile sites [12].

Regulatory relationships of RNU2

• Coexpression of the adenovirus 12 E1B 55 kDa oncoprotein and cellular tumor suppressor p53 is sufficient to induce metaphase fragility of the human RNU2 locus [13].

Analytical, diagnostic and therapeutic context of RNU2

• Using ectopic integration of engineered DNA arrays to create "new" fragile sites, we and others have previously shown that the transcriptionally competent U2 gene is necessary and sufficient for induction of fragility at the RNU2 locus upon infection of human cells with Adenovirus 12 [12].

References