BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20260708T074644EDT-1381nbdITX@132.216.98.100 DTSTAMP:20260708T114644Z DESCRIPTION:Dr. Jeffrey Wilusz\nProfessor\nColorado State University\nDepar tment of Microbiology\, Immunology & Pathology\n \n“How Viral RNAs Escape the Wrath of the Cellular RNA Decay\nMachinery during Infection”\n \n \nTh e mechanisms utilized by viruses to protect their transcripts\nfrom the ce llular RNA decay machinery\, as well as the biological\nrelevance of this protection\, are largely unexplored.  We have\nfound that Sindbis virus\, and likely other alphaviruses\, use U-rich\n3’ UTR sequences in their capp ed and polyadenylated RNAs to recruit\nthe cellular HuR protein during inf ections of both human and\nmosquito cells.   HuR binds viral RNAs with hig h\nspecificity and affinity.  Furthermore\, Sindbis virus induces\nthe sel ective movement of HuR protein out of the nucleus of\nmammalian cells duri ng infection thereby increasing the cytoplasmic\npool of the protein avail able to the virus.  Finally\,\nknockdown of HuR results in a significant i ncrease in the rate of\ndecay of Sindbis virus RNAs and diminishes viral y ields in both\nhuman and mosquito cells.  Collectively these data indicate \nthat Sindbis virus\, and likely other alphaviruses\, usurp the HuR\nprot ein to avoid the cellular mRNA decay machinery and maintain a\nhighly prod uctive infection.\nWe have also explored the relationship between the cell ular mRNA\ndecay machinery and two other RNA viruses.  Our results\nsugges t that non-polyadenylated flavivirus RNAs may repress the\nmajor 5’-3’ pat hway of cellular mRNA decay during infections via a\ndirect inhibition of the XRN1 5’-3’ exoribonuclease\, perhaps\ncontributing to viral pathogenes is.  Data on Rabies virus\, a\nnegative sense RNA virus\, suggest that the relative stability of\nits mRNAs\, in addition to the previously describe d efficiency of\ntranscription via start-stop polymerase initiation\, may play an\nimportant role in regulating the level of select viral mRNAs duri ng\ninfection.\n \n \nReferences\nBergman\, N\, Moraes KCM\, Anderson\, J. R.\, Zaric\, B.\, Kambach\, C\,\nSchneider\, R.J.\, Wilusz\, C.J. and Wilu sz J.  (2007)  Lsm\nproteins bind to and stabilize RNAs containing 5’ poly (A)\ntracts.  Nature Struct Mol. Biol.\,  14: 824-831.\n \nGarneau\, N.L.\ , Sokoloski\, K\, Opyrchal\, M\, Neff\, C.P.\, Wilusz\,\nC.J. and Wilusz\, J.  (2008).  The 3’ untranslated region\nof sindbis virus represses the d eadenylation of viral transcripts\nin mosquito and mammalian cells.  J. Vi rol. 82: \n880-892.\n \nSokoloski\, K\, Dickson\, A\, Chaskey E.L.\, Garne au\, N.L.\, Wilusz\,\nC.J. and Wilusz\, J.  (2010).  Sindbis virus usurps the\ncellular HuR protein to stabilize its transcripts and promote\nproduc tive infections in mammalian and mosquito cells.  In\nRevision\n DTSTART:20100329T160000Z DTEND:20100329T160000Z LOCATION:McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1Y6\, 3655 pr omenade Sir William Osler SUMMARY:Biochemistry Seminar URL:/channels/event/biochemistry-seminar-115234 END:VEVENT END:VCALENDAR