Loss of a newly discovered microRNA in Chinese hamster ovary cells leads to upregulation of N-glycolylneuraminic acid sialylation on monoclonal antibodies.
Chinese hamster ovary (CHO) cells
N-glycosylation
microRNA
monoclonal antibody
sialylation
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
10
12
2021
received:
07
06
2021
accepted:
11
12
2021
pubmed:
23
12
2021
medline:
5
4
2022
entrez:
22
12
2021
Statut:
ppublish
Résumé
Chinese hamster ovary (CHO) cells are known not to express appreciable levels of the sialic acid residue N-glycolylneuraminic acid (NGNA) on monoclonal antibodies. However, we actually have identified a recombinant CHO cell line expressing an IgG with unusually high levels of NGNA sialylation (>30%). Comprehensive multi-OMICs based experimental analyses unraveled the root cause of this atypical sialylation: (1) expression of the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene was spontaneously switched on, (2) CMAH mRNA showed an anti-correlated expression to the newly discovered Cricetulus griseus (cgr) specific microRNA cgr-miR-111 and exhibits two putative miR-111 binding sites, (3) miR-111 expression depends on the transcription of its host gene SDK1, and (4) a single point mutation within the promoter region of the sidekick cell adhesion molecule 1 (SDK1) gene generated a binding site for the transcriptional repressor histone H4 transcription factor HINF-P. The resulting transcriptional repression of SDK1 led to a downregulation of its co-expressed miR-111 and hence to a spontaneous upregulation of CMAH expression finally increasing NGNA protein sialylation.
Identifiants
pubmed: 34935124
doi: 10.1002/bit.28015
pmc: PMC9306616
doi:
Substances chimiques
Antibodies, Monoclonal
0
MicroRNAs
0
Neuraminic Acids
0
Recombinant Proteins
0
N-glycolylneuraminic acid
1113-83-3
N-Acetylneuraminic Acid
GZP2782OP0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
832-844Informations de copyright
© 2021 Boehringer Ingelheim Pharma GmbH & Co.KG. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
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