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@article{Salvato:2023:10.3389/fimmu.2023.1192028,
author = {Salvato, I and Ricciardi, L and Dal, Col J and Nigro, A and Giurato, G and Memoli, D and Sellitto, A and Lamparelli, EP and Crescenzi, MA and Vitale, M and Vatrella, A and Nucera, F and Brun, P and Caicci, F and Dama, P and Stiff, T and Castellano, L and Idrees, S and Johansen, MD and Faiz, A and Wark, PA and Hansbro, PM and Adcock, IM and Caramori, G and Stellato, C},
doi = {10.3389/fimmu.2023.1192028},
journal = {Frontiers in Immunology},
pages = {1--27},
title = {Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation},
url = {http://dx.doi.org/10.3389/fimmu.2023.1192028},
volume = {14},
year = {2023}
}

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TY  - JOUR
AB  - INTRODUCTION: The RNA-binding protein AU-rich-element factor-1 (AUF-1) participates to posttranscriptional regulation of genes involved in inflammation and cellular senescence, two pathogenic mechanisms of chronic obstructive pulmonary disease (COPD). Decreased AUF-1 expression was described in bronchiolar epithelium of COPD patients versus controls and in vitro cytokine- and cigarette smoke-challenged human airway epithelial cells, prompting the identification of epithelial AUF-1-targeted transcripts and function, and investigation on the mechanism of its loss. RESULTS: RNA immunoprecipitation-sequencing (RIP-Seq) identified, in the human airway epithelial cell line BEAS-2B, 494 AUF-1-bound mRNAs enriched in their 3'-untranslated regions for a Guanine-Cytosine (GC)-rich binding motif. AUF-1 association with selected transcripts and with a synthetic GC-rich motif were validated by biotin pulldown. AUF-1-targets' steady-state levels were equally affected by partial or near-total AUF-1 loss induced by cytomix (TNFα/IL1β/IFNγ/10 nM each) and siRNA, respectively, with differential transcript decay rates. Cytomix-mediated decrease in AUF-1 levels in BEAS-2B and primary human small-airways epithelium (HSAEC) was replicated by treatment with the senescence- inducer compound etoposide and associated with readouts of cell-cycle arrest, increase in lysosomal damage and senescence-associated secretory phenotype (SASP) factors, and with AUF-1 transfer in extracellular vesicles, detected by transmission electron microscopy and immunoblotting. Extensive in-silico and genome ontology analysis found, consistent with AUF-1 functions, enriched RIP-Seq-derived AUF-1-targets in COPD-related pathways involved in inflammation, senescence, gene regulation and also in the public SASP proteome atlas; AUF-1 target signature was also significantly represented in multiple transcriptomic COPD databases generated from primary HSAEC, from lung tissue and from single-cell RNA-sequ
AU  - Salvato,I
AU  - Ricciardi,L
AU  - Dal,Col J
AU  - Nigro,A
AU  - Giurato,G
AU  - Memoli,D
AU  - Sellitto,A
AU  - Lamparelli,EP
AU  - Crescenzi,MA
AU  - Vitale,M
AU  - Vatrella,A
AU  - Nucera,F
AU  - Brun,P
AU  - Caicci,F
AU  - Dama,P
AU  - Stiff,T
AU  - Castellano,L
AU  - Idrees,S
AU  - Johansen,MD
AU  - Faiz,A
AU  - Wark,PA
AU  - Hansbro,PM
AU  - Adcock,IM
AU  - Caramori,G
AU  - Stellato,C
DO  - 10.3389/fimmu.2023.1192028
EP  - 27
PY  - 2023///
SN  - 1664-3224
SP  - 1
TI  - Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation
T2  - Frontiers in Immunology
UR  - http://dx.doi.org/10.3389/fimmu.2023.1192028
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37483631
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2023.1192028/full
UR  - http://hdl.handle.net/10044/1/105624
VL  - 14
ER  -

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