Differentially processed human cytomegalovirus (HCMV) UL37 RNAs encode biologically significant proteins. Due to the recent discovery of alternative UL37 exon 3 (UL37x3) splice donors, permissively infected cells were thoroughly examined for additional alternatively spliced UL37 RNAs. Newly described donors within UL37 exon 1 (nt 52520) and intron 1 (nt 52209) as well as UL37x3 di (nt 50770) and dii (nt 50782) were differentially spliced to known downstream UL37 acceptors. The alternatively spliced UL37S, UL37L, UL37di and UL37dii RNAs predictably encode proteins of 83, 163, 217 and 213 residues, respectively, which share UL37x1 N-terminal sequences but differ downstream in their C termini. Moreover, temporal expression of the alternatively spliced UL37 RNAs differs during HCMV infection. The complexity of UL37 pre-mRNA processing is evidenced by the detection of 11 UL37 spliced and unspliced UL37x1 RNAs in HCMV-infected cells. Based upon these data, a revised HCMV UL37 gene map is presented, which incorporates all RNA species detected during permissive infection.
Al-BaraziH. O.,
Colberg-PoleyA. M.1996; The human cytomegalovirus UL37 immediate–early regulatory protein is an integral membrane N -glycoprotein which traffics through the endoplasmic reticulum and Golgi apparatus. J Virol 70:7198–7208
CheeM. S.,
BankierA. T.,
BeckS.12 other authors1990; Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Cur Top Microbiol Immunol 154:125–169
Colberg-PoleyA. M.1996; Functional roles of immediate early proteins encoded by the human cytomegalovirus UL36–38, UL115–119, TRS1/IRS1 and US3 loci. Intervirology 39:350–360
Colberg-PoleyA. M.,
SantomennaL. D.,
HarlowP. P.,
BenfieldP. A.,
TenneyD. J.1992; Human cytomegalovirus US3 and UL36–38 immediate–early proteins regulate gene expression. J Virol 66:95–105
Colberg-PoleyA. M.,
HuangL.,
SolteroV. E.,
IskenderianA.,
SchumacherR.-F.,
AndersD. G.1998; The acidic domain of pUL37x1 and gpUL37 plays a key role in transactivation of HCMV DNA replication gene promoter constructions. Virology 246:400–408
Colberg-PoleyA. M.,
PatelM. B.,
ErezoD. P. P.,
SlaterJ. E.2000; Human cytomegalovirus UL37 immediate–early regulatory proteins traffic through the secretory apparatus and to mitochondria. J Gen Virol 81:1779–1789
GoldmacherV. S.,
BartleL. M.,
SkaletskayaA.10 other authors1999; A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2. Proc Natl Acad Sci U S A 96:12536–12541
HayajnehW. A.,
Colberg-PoleyA. M.,
SkaletskayaA.,
BartleL. M.,
LesperanceM. M.,
Contopoulos-IoannidisD. G.,
KedershaN. L.,
GoldmacherV. S.2001a; The sequence and antiapoptotic functional domains of the human cytomegalovirus UL37 exon 1 immediate early protein are conserved in multiple primary strains. Virology 279:233–240
HayajnehW. A.,
Contopoulos-IoannidisD. G.,
LesperanceM. M.,
VenegasA. M.,
Colberg-PoleyA. M.2001b; The carboxyl terminus of the human cytomegalovirus UL37 immediate–early glycoprotein is conserved in primary strains and is important for transactivation. J Gen Virol 82:1569–1579
KouzaridesT.,
BankierA. T.,
SatchwellS. C.,
PreddyE.,
BarrellB. G.1988; An immediate early gene of human cytomegalovirus encodes a potential membrane glycoprotein. Virology 165:151–164 erratum 167, 326–327
MocarskiE. S.,
Tan CourcelleC.2001; Cytomegaloviruses and their replication. In Fields Virology , 4th edn. vol 2 pp 2629–2673 Edited by
KnipeD. M.,
HowleyP. M.
Philadelphia: Lippincott Williams & Wilkins;
RomanowskiM. J.,
ShenkT.1997; Characterization of the human cytomegalovirus irs1 and trs1 genes: a second immediate–early transcription unit within irs1 whose product antagonizes transcriptional activation. J Virol 71:1485–1496
ShirakataM.,
TerauchiM.,
AblikimM.,
ImadomeK.-I.,
HiraiK.,
AsoT.,
YamanashiY.2002; Novel immediate–early protein IE19 of human cytomegalovirus activates the origin recognition complex I promoter in a cooperative manner with IE72. J Virol 76:3158–3167
StenbergR. M.,
DeptoA. S.,
FortneyJ.,
NelsonJ. A.1989; Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate–early gene region. J Virol 63:2699–2708
SuY.,
TestaverdeJ. R.,
DavisC. N.,
HayajnehW. A.,
AdairR.,
Colberg-PoleyA. M.2003; Human cytomegalovirus UL37 immediate early target minigene RNAs are accurately spliced and polyadenylated. J Gen Virol 84:29–39
TenneyD. J.,
Colberg-PoleyA. M.1991a; Expression of the human cytomegalovirus UL36–38 immediate early region during permissive infection. Virology 182:199–210
TenneyD. J.,
Colberg-PoleyA. M.1991b; Human cytomegalovirus UL36–38 and US3 immediate early genes: temporally regulated expression of nuclear, cytoplasmic, and polysome-associated transcripts during infection. J Virol 65:6724–6734
TenneyD. J.,
SantomennaL. D.,
GoudieK. B.,
Colberg-PoleyA. M.1993; The human cytomegalovirus US3 immediate–early protein lacking the putative transmembrane domain regulates gene expression. Nucleic Acids Res 21:2931–2937
WinklerM.,
StammingerT.1996; A specific subform of the human cytomegalovirus transactivator protein pUL69 is contained within the tegument of virus particles. J Virol 70:8984–8987