Kew, Chun, Huang, Wenming, Fischer, Julia, Ganesan, Raja, Robinson, Nirmal ORCID: 0000-0002-7361-9491 and Antebi, Adam (2020). Evolutionarily conserved regulation of immunity by the splicing actor RNP-6/PUF60. eLife, 9. CAMBRIDGE: ELIFE SCIENCES PUBLICATIONS LTD. ISSN 2050-084X

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Abstract

Splicing is a vital cellular process that modulates important aspects of animal physiology, yet roles in regulating innate immunity are relatively unexplored. From genetic screens in C. elegans, we identified splicing factor RNP-6/PUF60 whose activity suppresses immunity, but promotes longevity, suggesting a tradeoff between these processes. Bacterial pathogen exposure affects gene expression and splicing in a rnp-6 dependent manner, and rnp-6 gain and loss-of-function activities reveal an active role in immune regulation. Another longevity promoting splicing factor, SFA-1, similarly exerts an immuno-suppressive effect, working downstream or parallel to RNP-6. RNP-6 acts through TIR-1/PMK-1/MAPK signaling to modulate immunity. The mammalian homolog, PUF60, also displays anti-inflammatory properties, and its levels swiftly decrease after bacterial infection in mammalian cells, implying a role in the host response. Altogether our findings demonstrate an evolutionarily conserved modulation of immunity by specific components of the splicing machinery.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kew, ChunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huang, WenmingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganesan, RajaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robinson, NirmalUNSPECIFIEDorcid.org/0000-0002-7361-9491UNSPECIFIED
Antebi, AdamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-329910
DOI: 10.7554/eLife.57591
Journal or Publication Title: eLife
Volume: 9
Date: 2020
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Place of Publication: CAMBRIDGE
ISSN: 2050-084X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; EXPRESSION; TRANSCRIPTION; LONGEVITY; PATHOGEN; PATHWAY; GENES; PUF60; ACTIVATIONMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32991

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