A new RNA element located in the coding region of a murine endogenous retrovirus can functionally replace the Rev/Rev-responsive element system in human immunodeficiency virus type 1 gag expression

Nuclear export of incompletely spliced RNAs is a prerequisite for retrovira l replication. Complex retroviruses like human immunodeficiency virus (HIV) encode a viral transport factor (Rev), which binds to its target sequence on the RNA genome and directs it into the Crm-1-mediated export pathway. Ot her retroviruses, like Mason-Pfizer monkey virus, contain cis-acting consti tutive RNA transport elements (CTE) which achieve nuclear export of intron- containing RNA via cellular transport factors. Here, we describe the identi fication and characterization of a novel cis-acting orientation-dependent R NA expression element in the coding region of the murine intracisternal A-t ype particle (IAP) MIA14. This IAP expression element (IAPE) can functional ly replace the Rev system in the expression of HIV-1 Gag proteins but funct ions independently of Crm-1. The presence of this element is needed for the expression of the IAP Gag proteins, indicating its biological significance . The IAPE can be functionally replaced by placing a CTE on the MIA14 RNA, further supporting its role in mRNA export. Northern blot analysis revealed that total RNA, as well as cytoplasmic RNA, was increased when the element was present. The element was mapped to a predicted stem-loop structure in the 3' part of the pol open reading frame. There was no overall homology be tween the LAPE and the CTE, but there was complete sequence identity betwee n short putative single-stranded loops. Deletion of these loops from the IA PE severely reduced Rev-independent Gag expression.