LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma.
EMBO Rep
; 24(6): e56282, 2023 06 05.
Article
de En
| MEDLINE
| ID: mdl-37009826
Human microproteins encoded by long non-coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493-encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA-binding protein PABPC4 and transferred to ribosomes for translation of a 95-amino-acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N-terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK-mediated AKT phosphorylation. Moreover, the formation of the SMIM26-AGK-SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493-encoded microprotein SMIM26 and establishes its anti-metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Néphrocarcinome
/
ARN long non codant
/
Tumeurs du rein
Limites:
Humans
Langue:
En
Journal:
EMBO Rep
Sujet du journal:
BIOLOGIA MOLECULAR
Année:
2023
Type de document:
Article
Pays d'affiliation:
Chine
Pays de publication:
Royaume-Uni