Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide

Abstract

Summary Emerging studies have linked the ribosome to more selective control of gene regulation. However, an outstanding question is whether ribosome heterogeneity at the level of core ribosomal proteins (RPs) exists and enables ribosomes to preferentially translate specific mRNAs genome-wide. Here, we measured the absolute abundance of RPs in translating ribosomes and profiled transcripts that are enriched or depleted from select subsets of ribosomes within embryonic stem cells. We find that heterogeneity in RP composition endows ribosomes with differential selectivity for translating subpools of transcripts including those controlling metabolism, cell cycle, and development. As an example, mRNAs enriched in binding to RPL10A/uL1-containing ribosomes are shown to require RPL10A/uL1 for their efficient translation. Within several of these transcripts, this level of regulation is mediated, at least in part, by internal ribosome entry sites. Together, these results reveal a critical functional link between ribosome heterogeneity and the post-transcriptional circuitry of gene expression.

The Flow of Information from Nucleus to Golgi Is Contingent upon Nuclear Membrane Synthesis and Protraction of the Ceramide-Containing Membrane to Endoplasmic Reticulum

“…As to the prevailing view of the existence of double and independent nuclear membranes separated by perinuclear space, the concept does not explain functional link of the inner nuclear membrane segments with cytosol. In our understanding of the intracellular membranes properties, and as our investigation suggest the segments recognized as is involved in restitution of the inner leaflet of the nuclear-ER membrane [40].…”

“…The nuclear outer membrane and ER are studded with ribosomes engaged in the protein renewal of the cell and its organelles [39] [40]. Our investigations on the assembly of the organelles-specific biomembranes reveal that the process is coordinated with simultaneous synthesis and intercalation of lipids that also commences in nuclear membrane and continues throughout ER.…”

“…The cell membranes designed on nucleus and ER, are revealed in the compartmentalization of the vast array of functions inaugurated in nucleus, and fulfilled by the cell organelles and cell membrane. On one facet the nuclear membrane gates multiplicity of highly coordinated processes that regulate nuclear mechanics and gene expression and provides strict platform for the recognition and transport of substances between nucleoplasm and cytoplasm, while on the opposing surface, it provides binding sites for the released to cytosol ribosomes that translate explicit mRNAs and faithfully recreate cell-specific proteins [39] [40]. Thus, the membrane barrier biogenesis and its components directly respond to the nuclear processes evoked by signaling.…”

“…By the extension, it is quite possible that the final destination markers for Golgi vesicles pathway integrated into the membrane at the stage of nuclear biomembrane assembly is quintessential in synthesis of the organelle-specific cargo in ER and its delivery to the exact site. This presumptive argument requires further exploration of other protein markers that accompany SPT in the vesicles containing SM and transporting cargo to basolateral epithelial segment of the cell membrane or endosomes and lysosomes [39] [40], and all is decided by the cluster of ribosomes that are simultaneously involved in the synthesis of the signal-demanded membranes and secretory products [41] [42].…”

“…The processes characterized by the investigations of ribosome footprints [39], heterogeneous ribosome distinct subpools [40] and the presence of the specific SPT on the inner and outer leaflet of ER imply that the placement of the specific lipids and protein is determined during early assembly of the membrane. The composition of the membrane and delivery of the synthetic cargo to the appropriate organelle are not relying on the process of flipping and flippases [46].…”