Redefining GBA gene structure unveils the ability of Cap-independent, IRES-dependent gene regulation.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
13 07 2022
13 07 2022
Historique:
received:
10
03
2020
accepted:
10
06
2022
entrez:
13
7
2022
pubmed:
14
7
2022
medline:
16
7
2022
Statut:
epublish
Résumé
Glucosylceramide is the primary molecule of glycosphingolipids, and its metabolic regulation is crucial for life. Defects in the catabolizing enzyme, glucocerebrosidase (GCase), cause a lysosomal storage disorder known as Gaucher disease. However, the genetic regulation of GCase has not been fully understood. Here we show the redefined structure of the GCase coding gene (GBA), and clarify the regulatory mechanisms of its transcription and translation. First, alternative uses of the two GBA gene promoters were identified in fibroblasts and HL60-derived macrophages. Intriguingly, both GBA transcripts and GCase activities were induced in macrophages but not in neutrophils. Second, we observed cap-independent translation occurs via unique internal ribosome entry site activities in first promoter-driven GBA transcripts. Third, the reciprocal expression was observed in GBA and miR22-3p versus GBAP1 transcripts before and after HL60-induced macrophage differentiation. Nevertheless, these findings clearly demonstrate novel cell-type-specific GBA gene expression regulatory mechanisms, providing new insights into GCase biology.
Identifiants
pubmed: 35831491
doi: 10.1038/s42003-022-03577-5
pii: 10.1038/s42003-022-03577-5
pmc: PMC9279297
doi:
Substances chimiques
Internal Ribosome Entry Sites
0
Glucosylceramidase
EC 3.2.1.45
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
639Informations de copyright
© 2022. The Author(s).
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