The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism.
5' Untranslated Regions
Cell Compartmentation
/ genetics
Cell Line, Tumor
Cell Proliferation
Cytosol
/ enzymology
Fibroblasts
/ cytology
Gene Expression Regulation
Glycine Hydroxymethyltransferase
/ genetics
Humans
Lymphocytes
/ cytology
Mitochondria
/ enzymology
Protein Binding
Protein Isoforms
/ genetics
RNA-Binding Proteins
/ genetics
Serine
/ metabolism
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
07 05 2019
07 05 2019
Historique:
accepted:
15
02
2019
revised:
01
02
2019
received:
05
09
2018
pubmed:
28
2
2019
medline:
26
11
2019
entrez:
28
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30809670
pii: 5365575
doi: 10.1093/nar/gkz129
pmc: PMC6486632
doi:
Substances chimiques
5' Untranslated Regions
0
Protein Isoforms
0
RNA-Binding Proteins
0
Serine
452VLY9402
Glycine Hydroxymethyltransferase
EC 2.1.2.1
SHMT protein, human
EC 2.1.2.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4240-4254Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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