RNA helicase A interacts with divergent lymphotropic retroviruses and promotes translation of human T-cell leukemia virus type 1.
The 5' untranslated region (UTR) of retroviruses contain structured replication motifs that impose barriers to efficient ribosome scanning. Two RNA structural motifs that facilitate efficient translation initiation despite a complex 5' UTR are internal ribosome entry site (IRES) and 5' proximal post-transcriptional control element (PCE). Here, stringent RNA and protein analyses determined the 5' UTR of spleen necrosis virus (SNV), reticuloendotheliosis virus A (REV-A) and human T-cell leukemia virus type 1 (HTLV-1) exhibit PCE activity, but not IRES activity. Assessment of SNV translation initiation in the natural context of the provirus determined that SNV is reliant on a cap-dependent initiation mechanism. Experiments with siRNAs identified that REV-A and HTLV-1 PCE modulate post-transcriptional gene expression through interaction with host RNA helicase A (RHA). Analysis of hybrid SNV/HTLV-1 proviruses determined SNV PCE facilitates Rex/Rex responsive element-independent Gag production and interaction with RHA is necessary. Ribosomal profile analyses determined that RHA is necessary for polysome association of HTLV-1 gag and provide direct evidence that RHA is necessary for efficient HTLV-1 replication. We conclude that PCE/RHA is an important translation regulatory axis of multiple lymphotropic retroviruses. We speculate divergent retroviruses have evolved a convergent RNA-protein interaction to modulate translation of their highly structured mRNA.
Bolinger
Cheryl
C
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210-1093, USA.
Yilmaz
Alper
A
Hartman
Tiffiney Roberts
TR
Kovacic
Melinda Butsch
MB
Fernandez
Soledad
S
Ye
Jianxin
J
Forget
Mary
M
Green
Patrick L
PL
Boris-Lawrie
Kathleen
K
D020121:5' Untranslated Regions / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D011533:Proviruses / Q000235:genetics / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism*; D012367:RNA, Viral / Q000737:chemistry*; D017986:Reticuloendotheliosis Viruses, Avian / Q000235:genetics*; D020079:Terminal Repeat Sequences; D053079:Trager duck spleen necrosis virus / Q000235:genetics
D020121:5' Untranslated Regions; D015683:Gene Products, gag; D012367:RNA, Viral; D020365:RNA Helicases