PMID- 36050755
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220916
IS  - 1741-7007 (Electronic)
IS  - 1741-7007 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Sep 1
TI  - NF90 interacts with components of RISC and modulates association of Ago2 with 
      mRNA.
PG  - 194
LID - 10.1186/s12915-022-01384-2 [doi]
LID - 194
AB  - BACKGROUND: Nuclear factor 90 (NF90) is a double-stranded RNA-binding protein 
      involved in a multitude of different cellular mechanisms such as transcription, 
      translation, viral infection, and mRNA stability. Recent data suggest that NF90 
      might influence the abundance of target mRNAs in the cytoplasm through miRNA- and 
      Argonaute 2 (Ago2)-dependent activity. RESULTS: Here, we identified the 
      interactome of NF90 in the cytoplasm, which revealed several components of the 
      RNA-induced silencing complex (RISC) and associated factors. 
      Co-immunoprecipitation analysis confirmed the interaction of NF90 with the 
      RISC-associated RNA helicase, Moloney leukemia virus 10 (MOV10), and other 
      proteins involved in RISC-mediated silencing, including Ago2. Furthermore, NF90 
      association with MOV10 and Ago2 was found to be RNA-dependent. Glycerol gradient 
      sedimentation of NF90 immune complexes indicates that these proteins occur in the 
      same protein complex. At target RNAs predicted to bind both NF90 and MOV10 in 
      their 3' UTRs, NF90 association was increased upon loss of MOV10 and vice versa. 
      Interestingly, loss of NF90 led to an increase in association of Ago2 as well as 
      a decrease in the abundance of the target mRNA. Similarly, during hypoxia, the 
      binding of Ago2 to vascular endothelial growth factor (VEGF) mRNA increased after 
      loss of NF90, while the level of VEGF mRNA decreased. CONCLUSIONS: These findings 
      reveal that, in the cytoplasm, NF90 can associate with components of RISC such as 
      Ago2 and MOV10. In addition, the data indicate that NF90 and MOV10 may compete 
      for the binding of common target mRNAs, suggesting a role for NF90 in the 
      regulation of RISC-mediated silencing by stabilizing target mRNAs, such as VEGF, 
      during cancer-induced hypoxia.
CI  - (c) 2022. The Author(s).
FAU - Grasso, Giuseppa
AU  - Grasso G
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France.
FAU - Akkawi, Charbel
AU  - Akkawi C
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France.
FAU - Franckhauser, Celine
AU  - Franckhauser C
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France.
FAU - Nait-Saidi, Rima
AU  - Nait-Saidi R
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France.
FAU - Bello, Maxime
AU  - Bello M
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France.
FAU - Barbier, Jerome
AU  - Barbier J
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France.
FAU - Kiernan, Rosemary
AU  - Kiernan R
AUID- ORCID: 0000-0001-6645-0686
AD  - UMR9002 CNRS-UM, Institut de Genetique Humaine-Universite de Montpellier, Gene 
      Regulation lab, 34396, Montpellier, France. Rosemary.Kiernan@igh.cnrs.fr.
LA  - eng
PT  - Journal Article
DEP - 20220901
PL  - England
TA  - BMC Biol
JT  - BMC biology
JID - 101190720
RN  - 0 (3' Untranslated Regions)
RN  - 0 (AGO2 protein, human)
RN  - 0 (Argonaute Proteins)
RN  - 0 (ILF3 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Nuclear Factor 90 Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Induced Silencing Complex)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.7.- (Mov10 protein, human)
RN  - EC 3.6.4.13 (RNA Helicases)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Argonaute Proteins/genetics/*metabolism
MH  - Humans
MH  - Hypoxia/genetics
MH  - MicroRNAs/metabolism
MH  - Nuclear Factor 90 Proteins/genetics/*metabolism
MH  - RNA Helicases/genetics/metabolism
MH  - RNA, Messenger/*metabolism
MH  - *RNA-Induced Silencing Complex/genetics/metabolism
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
PMC - PMC9438302
OTO - NOTNLM
OT  - Ago2
OT  - NF90
OT  - RIP
OT  - RISC
OT  - mRNA stability
COIS- The authors declare that they have no competing interests.
EDAT- 2022/09/02 06:00
MHDA- 2022/09/09 06:00
PMCR- 2022/09/01
CRDT- 2022/09/01 23:48
PHST- 2021/09/22 00:00 [received]
PHST- 2022/08/05 00:00 [accepted]
PHST- 2022/09/01 23:48 [entrez]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
PHST- 2022/09/01 00:00 [pmc-release]
AID - 10.1186/s12915-022-01384-2 [pii]
AID - 1384 [pii]
AID - 10.1186/s12915-022-01384-2 [doi]
PST - epublish
SO  - BMC Biol. 2022 Sep 1;20(1):194. doi: 10.1186/s12915-022-01384-2.