The mRNA-binding protein Serbp1 as an auxiliary protein associated with mammalian cytoplasmic ribosomes

Abstract

While transcription plays an obviously important role in gene expression, translation has recently been emerged as a key step that defines the composition and quality of the proteome in the cell of higher eukaryotes including mammals. Selective translation is supposed to be regulated by the structural heterogeneity of cytoplasmic ribosomes including differences in protein composition and chemical modifications. However, the current knowledge on the heterogeneity of mammalian ribosomes is limited. Here, we report mammalian Serbp1 as a ribosome-associated protein. The translated products of Serbp1 gene, including the longest isoform, were found to be localized in the nucleolus as well as in the cytoplasm. Subcellular fractionation indicated that most of cytoplasmic Serbp1 molecules were precipitated by ultracentrifugation. Proteomic analysis identified Serbp1 in the cytoplasmic ribosomes of the rodent testis. Polysome profiling suggested that Serbp1, as a component of the small 40S subunit, was included in translating ribosomes (polysomes). Cosedimentation of Serbp1 with the 40S subunit was observed after dissociation of the ribosomal subunits. Serbp1 was also included in the ribosomes of human cancer cells, which may lead to a mechanistic understanding of an emerging link between Serbp1 and tumour progression.

Significance of the study: In mammalian cells, the final protein output of their genetic program is determined not only by controlling transcription but also by regulating the posttranscriptional events. Although mRNA-binding proteins and the cytoplasmic ribosome have long been recognized as central players in the posttranscriptional regulation, their physical and functional interactions are still far from a complete understanding. Here, we describe the intracellular localization of Serbp1, an mRNA-binding protein, and the inclusion of this protein in actively translating ribosomes in normal and cancer cells. These findings shed a new light into molecular mechanisms underlying Serbp1 action in translational gene regulation and tumour progression.

Keywords: cytoplasmic ribosome; gene expression; isoform; mRNA-binding protein; malignant tumour; mammal; polysome; translational control.