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. In the eukaryotic cytoplasm, SRP co-translationally targets proteins to the endoplasmic reticulum and prevents misfolding and aggregation of the secretory proteins in the cytoplasm. It was demonstrated recently that SRP also possesses an earlier unknown function, the protection of mRNAs of secretory proteins from degradation. In this review, we analyze the progress in studies of SRPs from different organisms, SRP biogenesis, its structure, and function in protein targeting and mRNA protection.

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. The identification of specialized ribosomes requires evidence of the incorporation of different ribosomal proteins or of modifications to rRNA and/or protein that lead(s) to physiologically relevant changes in translation. In this review, we summarize ribosomal heterogeneity and specialization in mammals and discuss their relevance to several 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. If SRP recognizes the substrates but is unable to target them to ER, they may mislocalize or degrade. All these events lead to dramatic consequence for protein biogenesis, activating protein quality control pathways, and creating pressure on cell physiology, and might lead to the pathogenesis of disease. Indeed, SRP dysfunction is involved in many different human diseases, including: congenital neutropenia; idiopathic inflammatory myopathy; viral, protozoal, and prion infections; and cancer. In this work, we analyze diseases caused by SRP failure and discuss their possible molecular mechanisms.

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. In recent years, the heterogeneity and specialization of ribosomes have been widely reported in different eukaryotic study models; however, few reports on this topic have been made on protozoa and even less on protozoa parasites of medical importance. This review analyzes heterogeneities of ribosomes in protozoa parasites highlighting the specialization in their functions and their importance in parasitism, in the transition between stages in their life cycle, in the change of host and in response to environmental conditions.

The Signal Recognition Particle (SRP) targets secretory proteins to the endoplasmic reticulum (ER) for their subsequent transport and protects their mRNAs from degradation by the RAPP pathway. The SRP is an RNA-protein complex consisting of six protein subunits and one noncoding RNA assembled into S- and Alu-domains. However, the distinct roles of individual SRP subunits remain undetermined. Using a molecular dissection of the human SRP through the depletion of specific subunits, we demonstrate that S-domain subunits have a primary role in mRNA protection and protein targeting, while Alu-domain subunits are dispensable. The SRP54 subunit is essential for both processes and ribosome association, while other S-domain subunits (SRP19, SRP68, and SRP72) serve supportive roles. The expression of SRP subunits is dependent on each other within the same domains, suggesting independent domain assembly. These data provide new insights into the multidomain organization and distinct functions of human SRP subunits and establish a framework for understanding the molecular mechanisms of SRP-related human diseases.