The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism.
Nucleic Acids Res
; 47(8): 4240-4254, 2019 05 07.
Article
em En
| MEDLINE
| ID: mdl-30809670
ABSTRACT
Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Serina
/
Glicina Hidroximetiltransferase
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Proteínas de Ligação a RNA
/
Citosol
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Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália