Silencing of Aberrant Secretory Protein Expression by Disease-Associated Mutations.
Authors of this article are:
Tikhonova EB, Karamysheva ZN, von Heijne G, Karamyshev AL.
A summary of the article is shown below:
Signal recognition particle (SRP) recognizes signal sequences of secretory proteins and targets them to the endoplasmic reticulum membrane for translocation. Many human diseases are connected with defects in signal sequences. The current dogma states that the molecular basis of the disease-associated mutations in the secretory proteins is connected with defects in their transport. Here, we demonstrate for several secretory proteins with disease-associated mutations that the molecular mechanism is different from the dogma. Positively charged or helix-breaking mutations in the signal sequence hydrophobic core prevent synthesis of the aberrant proteins and lead to degradation of their mRNAs. The degree of mRNA depletion depends on the location and severity of the mutation in the signal sequence and correlates with inhibition of SRP interaction. Thus, SRP protects secretory protein mRNAs from degradation. The data demonstrate that if disease-associated mutations obstruct SRP interaction, they lead to silencing of the mutated protein expression.Copyright © 2019 Elsevier Ltd. All rights reserved.
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This article is a good source of information and a good way to become familiar with topics such as: protein quality control; protein synthesis and transport; signal recognition particle (SRP); signal sequence; translational control.