Circular IRE-type RNAs of the NR5A1 gene are formed in adrenocortical cells.
Adrenal Cortex
/ cytology
Adrenal Cortex Neoplasms
/ genetics
Base Sequence
Binding Sites
/ genetics
Cell Line, Tumor
Endoplasmic Reticulum Stress
Endoribonucleases
/ antagonists & inhibitors
Exons
Gene Expression
Humans
Models, Biological
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
RNA Splicing
RNA, Circular
/ biosynthesis
RNA, Messenger
/ genetics
Steroidogenic Factor 1
/ genetics
Sulfonamides
/ pharmacology
Thiophenes
/ pharmacology
Adrenal cortex
Circular RNA
NR5A1
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
received:
14
02
2019
accepted:
27
02
2019
pubmed:
12
3
2019
medline:
11
2
2020
entrez:
12
3
2019
Statut:
ppublish
Résumé
The recently discovered circular RNAs (circRNAs) are mostly formed by back-splicing where the downstream 5' splice site splices to the upstream 3' splice site by conventional pre-mRNA splicing. These circRNAs regulate gene expression by acting as sponges for micro-RNAs or RNA-binding proteins. Here we show that the NR5A1 (previously called Ad4BP or SF-1) gene which is exclusively expressed in the adrenal cortex and steroidogenic tissue can form atypical circRNAs by unconventional splicing. Two stem loops with inositol-requiring protein-1α (IRE1α) cleavage sites are connected by an IRE1α cleavage site to form a circRNA (circIRE RNA). From total RNA of normal human adrenal cortex, we detected a circIRE RNA with connected ends by IRE1α cleavage sites in exon 6 and exon 1 (circIRE NR5A1 ex6-1 RNA). circIRE NR5A1 ex6-1 RNA was not detected in the adrenocortical cancer cell line, H295R. When IRE1α was expressed in H295R cells a different circIRE NR5A1 RNA connecting IRE1-cleavage sites in exon 7 and exon 1 was detected (circIRE NR5A1 ex7-1 RNA). The expression of this circIRE RNA was inhibited by the IRE1 inhibitor 1, STF-083010, implicating that it was formed via the ER stress pathway, where IRE1α is a major factor. This is the first report of this type of circular RNA connected by IRE1-cleavage sites found to be expressed in mammalian cells in a tissue-specific manner. To our surprise, the concomitant expression of NR5A1 was increased by IRE1α implicating that NR5A1 was not subjected to IRE1-dependent decay of mRNA (RIDD) but rather activating a transcriptional regulatory network to cope with ER stress in steroidogenic tissue reminiscent to XBP1 in other tissue. We believe this is the first report of such tissue-specific transcriptional cascade responding to ER stress as well as the novel finding of circular RNAs connected by IRE1α cleavage sites expressed in mammalian tissue.
Identifiants
pubmed: 30853179
pii: S0006-291X(19)30366-3
doi: 10.1016/j.bbrc.2019.02.151
pii:
doi:
Substances chimiques
NR5A1 protein, human
0
RNA, Circular
0
RNA, Messenger
0
STF 083010
0
Steroidogenic Factor 1
0
Sulfonamides
0
Thiophenes
0
ERN1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-6Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.