Bunyamwera Orthobunyavirus S-Segment Untranslated Regions Mediate Poly(A) Tail-Independent Translation

被引:54
作者
Blakqori, Gjon [1 ]
van Knippenberg, Ingeborg [1 ]
Elliott, Richard M. [1 ]
机构
[1] Univ St Andrews, Sch Biol, Ctr Biomol Sci, St Andrews KY16 9ST, Fife, Scotland
基金
英国惠康基金;
关键词
NONSTRUCTURAL PROTEIN NSS; POLY(A)-BINDING PROTEIN; MESSENGER-RNAS; ROTAVIRUS INFECTION; BINDING-PROTEIN; VIRUS; NSP3; SEQUENCE; IDENTIFICATION; CALICIVIRUS;
D O I
10.1128/JVI.02201-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The mRNAs of Bunyamwera virus (BUNV), the prototype of the Bunyaviridae family, possess a 5' cap structure but lack a 3' poly(A) tail, a common feature of eukaryotic mRNAs that greatly enhances translation efficiency. Viral mRNAs also contain untranslated regions (UTRs) that flank the coding sequence. Using model virus-like mRNAs that harbor the Renilla luciferase reporter gene, we found that the 3' UTR of the BUNV small-segment mRNA mediated efficient translation in the absence of a poly(A) tail. Viral UTRs did not increase RNA stability, and polyadenylation did not significantly enhance reporter activity. Translation of virus-like mRNAs in transfected cells was unaffected by knockdown of poly(A)-binding protein (PABP) but was markedly reduced by depletion of eukaryotic initiation factor 4G, suggesting a PABP-independent process for translation initiation. In BUNV-infected cells, translation of polyadenylated but not virus-like mRNAs was inhibited. Furthermore, we demonstrate that the viral nucleocapsid protein binds to, and colocalizes with, PABP in the cytoplasm early in infection, followed by nuclear retention of PABP. Our results suggest that BUNV corrupts PABP function in order to inhibit translation of polyadenylated cellular mRNAs while its own mRNAs are translated in a PABP-independent process.
引用
收藏
页码:3637 / 3646
页数:10
相关论文
共 49 条
[1]   The human Poly(A)-binding protein 1 shuttles between the nucleus and the cytoplasm [J].
Afonina, E ;
Stauber, R ;
Pavlakis, GN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) :13015-13021
[2]   HIV protease cleaves poly(A)-binding protein [J].
Alvarez, E ;
Castelló, A ;
Menéndez-Arias, L ;
Carrasco, L .
BIOCHEMICAL JOURNAL, 2006, 396 :219-226
[3]  
Ausubel FM, 1992, CURRENT PROTOCOLS MO
[4]   Identification of the Bunyamwera bunyavirus transcription termination signal [J].
Barr, JN ;
Rodgers, JW ;
Wertz, GW .
JOURNAL OF GENERAL VIROLOGY, 2006, 87 :189-198
[5]   Efficient cDNA-based rescue of La Crosse bunyaviruses expressing or lacking the nonstructural protein NSs [J].
Blakqori, G ;
Weber, F .
JOURNAL OF VIROLOGY, 2005, 79 (16) :10420-10428
[6]   Bunyamwera bunyavirus nonstructural protein NSs is a nonessential gene product that contributes to viral pathogenesis [J].
Bridgen, A ;
Weber, F ;
Fazakerley, JK ;
Elliott, RM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (02) :664-669
[7]   Control of translation by the 5′- and 3′-terminal regions of the dengue virus genome [J].
Chiu, WW ;
Kinney, RM ;
Dreher, TW .
JOURNAL OF VIROLOGY, 2005, 79 (13) :8303-8315
[8]   A four-nucleotide translation enhancer in the 3′-terminal consensus sequence of the nonpolyadenylated mRNAs of rotavirus [J].
Chizhikov, V ;
Patton, JT .
RNA, 2000, 6 (06) :814-825
[9]   Specific isoforms of translation initiation factor 4GI show differences in translational activity [J].
Coldwell, Mark J. ;
Morley, Simon J. .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (22) :8448-8460
[10]  
Colón-Ramos DA, 2003, MOL BIOL CELL, V14, P4162, DOI 10.1091/mbc.E03-03-0139