期刊
MOLECULAR CELL
卷 67, 期 1, 页码 55-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2017.06.005
关键词
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资金
- Instituto de Salud Carlos III (ISCIII) [IIS10/00015, II12/00002]
- Spanish Ministry of Science and Innovation [SAF2014-52162-P]
- CIG European Commission [PCIG10-GA-2011-304160]
- NIH/National Cancer Institute [R01-CA158768]
- Asociacion Espanola Contra el Cancer [AECC GCB14-2035]
- ISCIII-RTICC [RD12/0036/0049]
- AGAUR [SGR 870]
- Ministerio de Economia y Competitividad, ISCIII [PI E13/00022]
- Spanish Ministry
- FEDER
- EMBO [ALTF 248-2012]
- IDIBELL
- Vall d'Hebron Institute of Oncology [IDIBELL-VHIO C15-074) VHIO]
- Ciencias Sem Fronteiras [249415]
- Juan de la Cierva Fellowship [FJCI-2014-20422]
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.
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