PMID- 27852861
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20190329
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 91
IP  - 3
DP  - 2017 Feb 1
TI  - Pre-mRNA Processing Factor Prp18 Is a Stimulatory Factor of Influenza Virus RNA 
      Synthesis and Possesses Nucleoprotein Chaperone Activity.
LID - 10.1128/JVI.01398-16 [doi]
LID - e01398-16
AB  - The genome of influenza virus (viral RNA [vRNA]) is associated with the 
      nucleoprotein (NP) and viral RNA-dependent RNA polymerases and forms helical 
      viral ribonucleoprotein (vRNP) complexes. The NP-vRNA complex is the biologically 
      active template for RNA synthesis by the viral polymerase. Previously, we 
      identified human pre-mRNA processing factor 18 (Prp18) as a stimulatory factor 
      for viral RNA synthesis using a Saccharomyces cerevisiae replicon system and a 
      single-gene deletion library of Saccharomyces cerevisiae (T. Naito, Y. Kiyasu, K. 
      Sugiyama, A. Kimura, R. Nakano, A. Matsukage, and K. Nagata, Proc Natl Acad Sci 
      USA, 104:18235-18240, 2007, https://doi.org/10.1073/pnas.0705856104). In infected 
      Prp18 knockdown (KD) cells, the synthesis of vRNA, cRNA, and viral mRNAs was 
      reduced. Prp18 was found to stimulate in vitro viral RNA synthesis through its 
      interaction with NP. Analyses using in vitro RNA synthesis reactions revealed 
      that Prp18 dissociates newly synthesized RNA from the template after the early 
      elongation step to stimulate the elongation reaction. We found that Prp18 
      functions as a chaperone for NP to facilitate the formation of NP-RNA complexes. 
      Based on these results, it is suggested that Prp18 accelerates influenza virus 
      RNA synthesis as an NP chaperone for the processive elongation reaction. 
      IMPORTANCE: Templates for viral RNA synthesis of negative-stranded RNA viruses 
      are not naked RNA but rather RNA encapsidated by viral nucleocapsid proteins 
      forming vRNP complexes. However, viral basic proteins tend to aggregate under 
      physiological ionic strength without chaperones. We identified the pre-mRNA 
      processing factor Prp18 as a stimulatory factor for influenza virus RNA 
      synthesis. We found that one of the targets of Prp18 is NP. Prp18 facilitates the 
      elongation reaction of viral polymerases by preventing the deleterious annealing 
      of newly synthesized RNA to the template. Prp18 functions as a chaperone for NP 
      to stimulate the formation of NP-RNA complexes. Based on these results, we 
      propose that Prp18 may be required to maintain the structural integrity of vRNP 
      for processive template reading.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Minakuchi, M
AU  - Minakuchi M
AD  - Department of Infection Biology, Graduate School of Comprehensive Human Sciences, 
      University of Tsukuba, Tsukuba, Japan.
FAU - Sugiyama, K
AU  - Sugiyama K
AD  - Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
FAU - Kato, Y
AU  - Kato Y
AD  - Department of Infection Biology, Graduate School of Comprehensive Human Sciences, 
      University of Tsukuba, Tsukuba, Japan.
FAU - Naito, T
AU  - Naito T
AD  - Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
FAU - Okuwaki, M
AU  - Okuwaki M
AUID- ORCID: 0000-0003-2118-442X
AD  - Department of Infection Biology, Graduate School of Comprehensive Human Sciences, 
      University of Tsukuba, Tsukuba, Japan.
AD  - Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
FAU - Kawaguchi, A
AU  - Kawaguchi A
AD  - Department of Infection Biology, Graduate School of Comprehensive Human Sciences, 
      University of Tsukuba, Tsukuba, Japan.
AD  - Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
FAU - Nagata, K
AU  - Nagata K
AD  - Faculty of Medicine, University of Tsukuba, Tsukuba, Japan 
      knagata@md.tsukuba.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20170118
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Nucleoproteins)
RN  - 0 (PRPF18 protein, human)
RN  - 0 (RNA Splicing Factors)
RN  - 0 (RNA, Viral)
RN  - 0 (Ribonucleoproteins)
SB  - IM
MH  - Cell Line
MH  - Cells, Cultured
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Influenza A virus/*physiology
MH  - Influenza, Human/genetics/*metabolism/*virology
MH  - Nucleoproteins/*metabolism
MH  - Protein Binding
MH  - RNA Splicing Factors/genetics/*metabolism
MH  - RNA, Viral/*biosynthesis
MH  - Ribonucleoproteins/metabolism
MH  - Transcription Elongation, Genetic
MH  - Transcription, Genetic
PMC - PMC5244316
OTO - NOTNLM
OT  - host factor
OT  - protein chaperones
OT  - ribonucleoprotein
OT  - viral RNA synthesis
EDAT- 2016/11/18 06:00
MHDA- 2017/05/16 06:00
PMCR- 2017/07/18
CRDT- 2016/11/18 06:00
PHST- 2016/07/13 00:00 [received]
PHST- 2016/11/13 00:00 [accepted]
PHST- 2016/11/18 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2016/11/18 06:00 [entrez]
PHST- 2017/07/18 00:00 [pmc-release]
AID - JVI.01398-16 [pii]
AID - 01398-16 [pii]
AID - 10.1128/JVI.01398-16 [doi]
PST - epublish
SO  - J Virol. 2017 Jan 18;91(3):e01398-16. doi: 10.1128/JVI.01398-16. Print 2017 Feb 
      1.