The translational capability of ribosomes deprived of specific nonfunda-mental ribosomal proteins may be altered. Physiological mechanisms are scanty, and it is unclear whether free ribosomal proteins can cross talk with the signaling machinery. RACK1 (receptor for activated C kinase 1) is a highly conserved scaffold protein, located on the 40S subunit near the mRNA exit channel. RACK1 is involved in a variety of intracellular contexts, both on and off the ribosomes, acting as a receptor for proteins in signaling, such as the protein kinase C (PKC) family. Here we show that the binding of RACK1 to ribosomes is essential for full translation of capped mRNAs and efficient recruitment of eukaryotic initiation factor 4E (eIF4E). In vitro, when RACK1 is partially depleted, supplementing the ribosome machinery with wild-type RACK1 restores the translational capability, whereas the addition of a RACK1 mutant that is unable to bind ribosomes does not. Outside the ribosome, RACK1 has a reduced half-life. By accumulating in living cells, free RACK1 exerts an inhibitory phenotype, impairing cell cycle progression and repressing global translation. Here we present RACK1 binding to ribosomes as a crucial way to regulate translation, possibly through interaction with known partners on or off the ribosome that are involved in signaling.
Rack1 specifically regulates translation through its binding to ribosomes / S. Gallo, S. Ricciardi, N. Manfrini, S. Oliveto, P. Calamita, M. Mancino, E. Maffioli, M. Moro, M. Crosti, V. Berno, M. Bombaci, G. Tedeschi, E. Pesce, S. Biffo. - In: MOLECULAR AND CELLULAR BIOLOGY. - ISSN 0270-7306. - 38:23(2018 Dec).
|Titolo:||Rack1 specifically regulates translation through its binding to ribosomes|
|Parole Chiave:||Cell signaling; EIF4E; EIF6; mRNA; PKC; Puromycin; RACK1; Ribosomes; Stress; Translational control; Molecular Biology; Cell Biology|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
Settore BIO/06 - Anatomia Comparata e Citologia
|Progetto:||Noncoding and Translational Modulation of Gene Expression and Epigenetic Changes|
Molecular linkage between translation,epigenetic changes and metabolism and the development of insulin resistance
|Data di pubblicazione:||dic-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1128/MCB.00230-18|
|Appare nelle tipologie:||01 - Articolo su periodico|