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SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites

Lakkaraju, Asvin K K.
Johnson, Arthur E.
Published in Cell. 2008, vol. 133, no. 3, p. 440-51
Abstract SRP is essential for targeting nascent chains to the endoplasmic reticulum, and it delays nascent chain elongation in cell-free translation systems. However, the significance of this function has remained unclear. We show that efficient protein translocation into the ER is incompatible with normal cellular translation rates due to rate-limiting concentrations of SRP receptor (SR). We complemented mammalian cells depleted of SRP14 by expressing mutant versions of the protein lacking the elongation arrest function. The absence of a delay caused inefficient targeting of preproteins leading to defects in secretion, depletion of proteins in the endogenous membranes, and reduced cell growth. The detrimental effects were reversed by either reducing the cellular protein synthesis rate or increasing SR expression. SRP therefore ensures that nascent chains remain translocation competent during the targeting time window dictated by SR. Since SRP-signal sequence affinities vary, the delay may also regulate which proteins are preferentially targeted.
Keywords AnimalsCell CycleCell LineCell-Free SystemEndoplasmic Reticulum : RoughGreen Fluorescent ProteinsHela CellsHumansMolecular Sequence DataPeptide Chain Elongation : TranslationalProtein Synthesis InhibitorsProtein TransportSignal Recognition Particle
PMID: 18455985
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LAKKARAJU, Asvin K K. et al. SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites. In: Cell, 2008, vol. 133, n° 3, p. 440-51. doi: 10.1016/j.cell.2008.02.049 https://archive-ouverte.unige.ch/unige:661

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Deposited on : 2009-01-28

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