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Updated: Feb 27, 2026

Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
Published on: May 10, 2018
Autogenous Control of 5′TOP mRNA Stability by 40S Ribosomes
Antonio Gentilella1, Francisco D Morón-Duran2, Pedro Fuentes2
1Metabolism and Cancer Group, Molecular Mechanisms And Experimental Therapy In Oncology Program, Bellvitge Biomedical Research Institute, IDIBELL, 08908 Barcelona, Spain; Department of Biochemistry and Physiology, Faculty of Pharmacy, Universitat de Barcelona, 08028 Barcelona, Spain.
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.
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