Pathogenic signal peptide variants in the human genome.

Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized.

Ribosome Specialization in Protozoa Parasites.

Ribosomes, in general, are viewed as constitutive macromolecular machines where protein synthesis takes place; however, this view has been recently challenged, supporting the hypothesis of ribosome specialization and opening a completely new field of research. Recent studies have demonstrated that ribosomes are heterogenous in their nature and can provide another layer of gene expression control by regulating translation. Heterogeneities in ribosomal RNA and ribosomal proteins that compose them favor the selective translation of different sub-pools of mRNAs and functional specialization.

Specialized Ribosomes in Health and Disease.

Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, and occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or specific changes to the ribosome that regulate the translation of a specific group of transcripts. These alterations have been shown to affect the affinity of ribosomes for certain mRNAs or change the cotranslational folding of nascent polypeptides at the exit tunnel.

Defective Human SRP Induces Protein Quality Control and Triggers Stress Response.

Regulation of Aberrant Protein Production (RAPP) is a protein quality control in mammalian cells. RAPP degrades mRNAs of nascent proteins not able to associate with their natural interacting partners during synthesis at the ribosome. However, little is known about the molecular mechanism of the pathway, its substrates, or its specificity.

Signal Recognition Particle in Human Diseases.

The signal recognition particle (SRP) is a ribonucleoprotein complex with dual functions. It co-translationally targets proteins with a signal sequence to the endoplasmic reticulum (ER) and protects their mRNA from degradation. If SRP is depleted or cannot recognize the signal sequence, then the Regulation of Aberrant Protein Production (RAPP) is activated, which results in the loss of secretory protein mRNA.

SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection.

Signal recognition particle (SRP) is an RNA and protein complex that exists in all domains of life. It consists of one protein and one noncoding RNA in some bacteria. It is more complex in eukaryotes and consists of six proteins and one noncoding RNA in mammals.