Identification of a gamma interferon-activated inhibitor of translation-like RNA motif at the 3' end of the transmissible gastroenteritis coronavirus genome modulating innate immune response

MBio
Silvia Marquez-JuradoFernando Almazán

Abstract

A 32-nucleotide (nt) RNA motif located at the 3' end of the transmissible gastroenteritis coronavirus (TGEV) genome was found to specifically interact with the host proteins glutamyl-prolyl-tRNA synthetase (EPRS) and arginyl-tRNA synthetase (RRS). This RNA motif has high homology in sequence and secondary structure with the gamma interferon-activated inhibitor of translation (GAIT) element, which is located at the 3' end of several mRNAs encoding proinflammatory proteins. The GAIT element is involved in the translation silencing of these mRNAs through its interaction with the GAIT complex (EPRS, heterogeneous nuclear ribonucleoprotein Q, ribosomal protein L13a, and glyceraldehyde 3-phosphate dehydrogenase) to favor the resolution of inflammation. Interestingly, we showed that the viral RNA motif bound the GAIT complex and inhibited the in vitro translation of a chimeric mRNA containing this RNA motif. To our knowledge, this is the first GAIT-like motif described in a positive RNA virus. To test the functional role of the GAIT-like RNA motif during TGEV infection, a recombinant coronavirus harboring mutations in this motif was engineered and characterized. Mutations of the GAIT-like RNA motif did not affect virus growth in cell ...Continue Reading

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Citations

Jan 14, 2017·Journal of Nucleic Acids·Divya Khandige SharmaNehal Thakor
Nov 30, 2019·Cell Death & Disease·Anzheng NieDongsheng Yu
Nov 21, 2017·Wiley Interdisciplinary Reviews. RNA·Abul ArifPaul L Fox
Oct 19, 2021·Frontiers in Cell and Developmental Biology·Prajna NayakGirish S Ratnaparkhi

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Methods Mentioned

BETA
pulldown
immunoprecipitation
PCR
immunoprecipitation assay
electrophoretic mobility shift assay
electrophoresis
pull down
transfection
PCRs
in vitro transcription

Software Mentioned

Mfold
7500

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