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The synthesis of ribosomal proteins (RPs) has long been known to be a process strongly linked to the growth status of the cell. In vertebrates, this coordination is dependent on RP mRNA translational efficiency, which changes according to physiological circumstances. | ỊFEBS Journal REVIEW ARTICLE Synthesis and function of ribosomal proteins - fading models and new perspectives Sara Caldarola Maria Chiara De Stefano Francesco Amaldi and Fabrizio Loreni Department of Biology University Tor Vergata Roma Italy Keywords mTOR signaling nucleolus protein synthesis protein turnover ribosomal pathology ribosomalstress ribosome biogenesis TOP mRNA translationalcontrol Correspondence F. Loreni Department of Biology University Tor Vergata Via Ricerca Scientifica 00133 Roma Italy Fax 39 062023500 Tel 39 0672594317 E-mail loreni@uniroma2.it Received 16 February 2009 revised 18 March 2009 accepted 2 April2009 doi 10.1111 j.1742-4658.2009.07036.x The synthesis of ribosomal proteins RPs has long been known to be a process strongly linked to the growth status of the cell. In vertebrates this coordination is dependent on RP mRNA translational efficiency which changes according to physiological circumstances. Despite many years of investigation the trans-acting factors and the signaling pathways involved in this regulation are still elusive. At the same time however new techniques and classic approaches have opened up new perspectives as regards RP regulation and function. In fact the proteasome seems to play a crucial and unpredicted role in regulating the availability of RPs for subunit assembly. In addition the study of human ribosomal pathologies and animal models for these diseases has revealed that perturbation in the synthesis and or function of an RP activates a p53-dependent stress response. Surprisingly the effect of the ribosomal stress is more dramatic in specific physiological processes hemopoiesis in humans and pigmentation in mice. Moreover alteration of each RP impacts differently on the development of an organism. Introduction Ribosomal proteins RPs are fundamental components of ribosomes. They assemble with four rRNA molecules in a complex process that takes place sequentially in the nucleolus in the nucleoplasm and in the .