PMID- 29152905
OWN - NLM
STAT- MEDLINE
DCOM- 20180924
LR  - 20220129
IS  - 1757-7012 (Electronic)
IS  - 1757-7004 (Print)
IS  - 1757-7004 (Linking)
VI  - 9
IP  - 2
DP  - 2018 Mar
TI  - The GAIT translational control system.
LID - 10.1002/wrna.1441 [doi]
LID - e1441
AB  - The interferon (IFN)-gamma-activated inhibitor of translation (GAIT) system directs 
      transcript-selective translational control of functionally related genes. In 
      myeloid cells, IFN-gamma induces formation of a multiprotein GAIT complex that binds 
      structural GAIT elements in the 3'-untranslated regions (UTRs) of multiple 
      inflammation-related mRNAs, including ceruloplasmin and VEGF-A, and represses 
      their translation. The human GAIT complex is a heterotetramer containing 
      glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), 
      ribosomal protein L13a (L13a), and glyceraldehyde-3-phosphate dehydrogenase 
      (GAPDH). A network of IFN-gamma-stimulated kinases regulates recruitment and assembly 
      of GAIT complex constituents. Activation of cyclin-dependent kinase 5 (Cdk5), 
      mammalian target of rapamycin complex 1 (mTORC1), and S6K1 kinases induces EPRS 
      release from its parental multiaminoacyl tRNA synthetase complex to join NSAP1 in 
      a 'pre-GAIT' complex. Subsequently, the DAPK-ZIPK kinase axis phosphorylates 
      L13a, inducing release from the 60S ribosomal subunit and binding to GAPDH. The 
      subcomplexes join to form the functional GAIT complex. Each constituent has a 
      distinct role in the GAIT system. EPRS binds the GAIT element in target mRNAs, 
      NSAP1 negatively regulates mRNA binding, L13a binds eIF4G to block ribosome 
      recruitment, and GAPDH shields L13a from proteasomal degradation. The GAIT system 
      is susceptible to genetic and condition-specific regulation. An N-terminus EPRS 
      truncate is a dominant-negative inhibitor ensuring a 'translational trickle' of 
      target transcripts. Also, hypoxia and oxidatively modified lipoproteins regulate 
      GAIT activity. Mouse models exhibiting absent or genetically modified GAIT 
      complex constituents are beginning to elucidate the physiological role of the 
      GAIT system, particularly in the resolution of chronic inflammation. Finally, 
      GAIT-like systems in proto-chordates suggests an evolutionarily conserved role of 
      the pathway in innate immunity. WIREs RNA 2018, 9:e1441. doi: 10.1002/wrna.1441 
      This article is categorized under: Translation > Translation Regulation RNA 
      Interactions with Proteins and Other Molecules > RNA-Protein Complexes Regulatory 
      RNAs/RNAi/Riboswitches > Riboswitches.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Arif, Abul
AU  - Arif A
AD  - Department of Cellular and Molecular Medicine, Lerner Research Institute, 
      Cleveland Clinic, Cleveland, OH, USA.
FAU - Yao, Peng
AU  - Yao P
AD  - Aab Cardiovascular Research Institute, University of Rochester School of Medicine 
      & Dentistry, Rochester, NY, USA.
FAU - Terenzi, Fulvia
AU  - Terenzi F
AD  - Department of Cellular and Molecular Medicine, Lerner Research Institute, 
      Cleveland Clinic, Cleveland, OH, USA.
FAU - Jia, Jie
AU  - Jia J
AD  - Department of Cellular and Molecular Medicine, Lerner Research Institute, 
      Cleveland Clinic, Cleveland, OH, USA.
FAU - Ray, Partho Sarothi
AU  - Ray PS
AD  - Department of Biological Sciences, Indian Institute of Science Education and 
      Research, Kolkata, India.
FAU - Fox, Paul L
AU  - Fox PL
AD  - Department of Cellular and Molecular Medicine, Lerner Research Institute, 
      Cleveland Clinic, Cleveland, OH, USA.
LA  - eng
GR  - 500139-Z-09-Z/WTDBT_/DBT-Wellcome Trust India Alliance/India
GR  - R01 GM115476/GM/NIGMS NIH HHS/United States
GR  - R01 GM086430/GM/NIGMS NIH HHS/United States
GR  - P01 HL076491/HL/NHLBI NIH HHS/United States
GR  - P01 HL029582/HL/NHLBI NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - WT500139/Z/09/Z/WTDBT_/DBT-Wellcome Trust India Alliance/India
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20171120
PL  - United States
TA  - Wiley Interdiscip Rev RNA
JT  - Wiley interdisciplinary reviews. RNA
JID - 101536955
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Heterogeneous-Nuclear Ribonucleoproteins)
RN  - 0 (Ribosomal Proteins)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 6.1.1.- (Amino Acyl-tRNA Synthetases)
RN  - EC 6.1.1.- (glutamyl-prolyl-tRNA synthetase)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Amino Acyl-tRNA Synthetases/*metabolism
MH  - Animals
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism
MH  - Heterogeneous-Nuclear Ribonucleoproteins/*metabolism
MH  - Humans
MH  - Interferon-gamma/*metabolism
MH  - *Protein Biosynthesis
MH  - Ribosomal Proteins/*metabolism
PMC - PMC5815886
MID - NIHMS903865
EDAT- 2017/11/21 06:00
MHDA- 2018/09/25 06:00
PMCR- 2020/04/20
CRDT- 2017/11/21 06:00
PHST- 2017/03/31 00:00 [received]
PHST- 2017/07/12 00:00 [revised]
PHST- 2017/07/31 00:00 [accepted]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2018/09/25 06:00 [medline]
PHST- 2017/11/21 06:00 [entrez]
PHST- 2020/04/20 00:00 [pmc-release]
AID - WRNA1441 [pii]
AID - 10.1002/wrna.1441 [doi]
PST - ppublish
SO  - Wiley Interdiscip Rev RNA. 2018 Mar;9(2):e1441. doi: 10.1002/wrna.1441. Epub 2017 
      Nov 20.