title: Rotavirus prevents the expression of host responses by blocking the nucleocytoplasmic transport of polyadenylated mRNAs.
abstract: Rotaviruses are the most important agent of severe gastroenteritis in young children. Early in infection, these viruses take over the host translation machinery, causing a severe shutoff of cell protein synthesis while viral proteins are efficiently synthesized. In infected cells, there is an accumulation of the cytoplasmic poly(A)-binding protein in the nucleus, induced by the viral protein NSP3. Here we found that poly(A)-containing mRNAs also accumulate and become hyperadenylated in the nuclei of infected cells. Using reporter genes bearing the untranslated regions (UTRs) of cellular or viral genes, we found that the viral UTRs do not determine the efficiency of translation of mRNAs in rotavirus-infected cells. Furthermore, we showed that while a polyadenylated reporter mRNA directly delivered into the cytoplasm of infected cells was efficiently translated, the same reporter introduced as a plasmid that needs to be transcribed and exported to the cytoplasm was poorly translated. Altogether, these results suggest that nuclear retention of poly(A)-containing mRNAs is one of the main strategies of rotavirus to control cell translation and therefore the host antiviral and stress responses.
authors.affiliation: Departamento de Génetica del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Rubio
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Mora
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Arias
authors.forename: Susana
authors.initials: S
authors.lastname: López
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012401:Rotavirus / Q000235:genetics / Q000378:metabolism*; D012400:Rotavirus Infections / Q000235:genetics* / Q000378:metabolism* / Q000821:virology
chemical_list: D012333:RNA, Messenger
references.citation: Mol Cell. 2005 Jan 7;17(1):93-102
references.pmid: 15629720
references.citation: Mol Cell Biol. 2010 Nov;30(21):4996-5008
references.pmid: 20823266
references.citation: Biochem J. 2010 Jan 27;426(1):1-12
references.pmid: 20102337
references.citation: J Mol Biol. 1979 Jun 25;131(2):353-73
references.pmid: 226719
references.citation: Mol Cell Biol. 2011 Aug;31(15):3113-25
references.pmid: 21646427
references.citation: Mol Cell Biol. 1986 Aug;6(8):2932-43
references.pmid: 3537727
references.citation: PLoS Biol. 2009 May 5;7(5):e1000107
references.pmid: 19468299
references.citation: J Biol Chem. 1998 May 22;273(21):13015-21
references.pmid: 9582337
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1853-8
references.pmid: 17267598
references.citation: J Virol. 2006 Sep;80(18):9031-8
references.pmid: 16940515
references.citation: J Virol. 2009 Sep;83(17):8819-31
references.pmid: 19553303
references.citation: J Cell Sci. 2005 Jun 1;118(Pt 11):2425-33
references.pmid: 15923655
references.citation: Emerg Infect Dis. 2003 May;9(5):565-72
references.pmid: 12737740
references.citation: Nucleic Acids Res. 1995 Jun 25;23(12):2198-205
references.pmid: 7610048
references.citation: J Virol. 2010 Sep;84(17):8539-48
references.pmid: 20573819
references.citation: J Virol. 2008 Jun;82(11):5368-80
references.pmid: 18385250
references.citation: J Virol. 2005 Jan;79(1):184-92
references.pmid: 15596814
references.citation: J Virol. 1993 Jun;67(6):3159-65
references.pmid: 8388495
references.citation: J Virol. 2008 Nov;82(22):11283-93
references.pmid: 18799579
references.citation: J Cell Sci. 2009 Oct 15;122(Pt 20):3799-809
references.pmid: 19789179
references.citation: Chromosoma. 2006 Apr;115(2):98-109
references.pmid: 16421734
references.citation: Genome Biol. 2003;4(7):223
references.pmid: 12844354
references.citation: J Virol. 2010 Sep;84(18):9161-9
references.pmid: 20631149
references.citation: PLoS Pathog. 2011 Jul;7(7):e1002150
references.pmid: 21811408
references.citation: Mol Cell Biol. 1989 Nov;9(11):5073-80
references.pmid: 2601709
references.citation: J Virol. 2008 Feb;82(3):1496-504
references.pmid: 18032499
references.citation: Mol Cell. 2002 Jun;9(6):1273-83
references.pmid: 12086624
references.citation: Mol Cell Biol. 2008 Apr;28(8):2648-58
references.pmid: 18250159
references.citation: J Virol. 2000 Aug;74(15):7064-71
references.pmid: 10888646
references.citation: Science. 1997 Jun 20;276(5320):1845-8
references.pmid: 9188527
references.citation: EMBO J. 1998 Oct 1;17(19):5811-21
references.pmid: 9755181
references.citation: Nature. 2008 Jun 26;453(7199):1276-80
references.pmid: 18496529
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Virology. 2002 Mar 30;295(1):190-200
references.pmid: 12033777
references.citation: J Gen Virol. 2012 Jul;93(Pt 7):1483-1494
references.pmid: 22442114
references.citation: J Virol. 2009 Apr;83(8):3637-46
references.pmid: 19193790
references.citation: J Virol. 2011 Dec;85(23):12594-604
references.pmid: 21937647
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7029-36
references.pmid: 11416183
references.citation: Arch Virol. 1998;143(5):981-96
references.pmid: 9645203
references.citation: J Virol. 1999 Jul;73(7):5411-21
references.pmid: 10364288
references.citation: RNA. 2000 Jun;6(6):814-25
references.pmid: 10864041
references.citation: EMBO J. 2001 Jan 15;20(1-2):240-9
references.pmid: 11226174
references.citation: Cold Spring Harb Symp Quant Biol. 2001;66:293-300
references.pmid: 12762031
references.citation: Cell. 2002 Feb 22;108(4):545-56
references.pmid: 11909525