Stability of the long noncoding-polyadenylated nuclear (PAN) RNA from Kaposi's 
sarcoma-associated herpesvirus is conferred by an expression and nuclear 
retention element (ENE). The ENE protects PAN RNA from a rapid 
deadenylation-dependent decay pathway via formation of a triple helix between 
the U-rich internal loop of the ENE and the 3'-poly(A) tail. Because viruses 
borrow molecular mechanisms from their hosts, we searched highly abundant human 
long-noncoding RNAs and identified putative ENE-like structures in 
metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and multiple 
endocrine neoplasia-β (MENβ) RNAs. Unlike the PAN ENE, the U-rich internal loops 
of both predicted cellular ENEs are interrupted by G and C nucleotides and 
reside upstream of genomically encoded A-rich tracts. We confirmed the ability 
of MALAT1 and MENβ sequences containing the predicted ENE and A-rich tract to 
increase the levels of an intronless β-globin reporter RNA. UV thermal 
denaturation profiles at different pH values support formation of a 
triple-helical structure composed of multiple U•A-U base triples and a single 
C•G-C base triple. Additional analyses of the MALAT1 ENE revealed that robust 
stabilization activity requires an intact triple helix, strong stems at the 
duplex-triplex junctions, a G-C base pair flanking the triplex to mediate 
potential A-minor interactions, and the 3'-terminal A of the A-rich tract to 
form a blunt-ended triplex lacking unpaired nucleotides at the duplex-triplex 
junction. These examples of triple-helical, ENE-like structures in cellular 
noncoding RNAs, are unique.