Autogenous Control of 5'TOP mRNA Stability by 40S Ribosomes.
Mol Cell
; 67(1): 55-70.e4, 2017 07 06.
Article
en En
| MEDLINE
| ID: mdl-28673543
ABSTRACT
Ribosomal protein (RP) expression in higher eukaryotes is regulated translationally through the 5'TOP sequence. This mechanism evolved to more rapidly produce RPs on demand in different tissues. Here we show that 40S ribosomes, in a complex with the mRNA binding protein LARP1, selectively stabilize 5'TOP mRNAs, with disruption of this complex leading to induction of the impaired ribosome biogenesis checkpoint (IRBC) and p53 stabilization. The importance of this mechanism is underscored in 5q− syndrome, a macrocytic anemia caused by a large monoallelic deletion, which we found to also encompass the LARP1 gene. Critically, depletion of LARP1 alone in human adult CD34+ bone marrow precursor cells leads to a reduction in 5'TOP mRNAs and the induction of p53. These studies identify a 40S ribosome function independent of those in translation that, with LARP1, mediates the autogenous control of 5'TOP mRNA stability, whose disruption is implicated in the pathophysiology of 5q− syndrome.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ribonucleoproteínas
/
Proteínas Ribosómicas
/
Ribosomas
/
Autoantígenos
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Biosíntesis de Proteínas
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ARN Mensajero
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Estabilidad del ARN
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Secuencia de Oligopirimidina en la Región 5' Terminal del ARN
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2017
Tipo del documento:
Article