Similar Datasets
Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.
2018-04-05 | GSE96594 | GEO
Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.
2018-04-05 | GSE96593 | GEO
Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.
2018-04-05 | GSE96555 | GEO
Project description:Coordinated control of mRNA and rRNA processing regulates early mammalian embryogenesis
| PRJNA379118 | ENA
Project description:Ribosomal RNA (rRNA) is co- and post-transcriptionally processed into active ribosomes. This process is dynamically regulated by direct covalent modifications of the polymerase that synthesizes the rRNA, RNA polymerase I (Pol I), and by interactions with cofactors that influence initiation, elongation, and termination activities of Pol I. The rate of transcription elongation by Pol I directly influences processing of nascent rRNA, and changes in Pol I transcription rate result in alternative rRNA processing events that lead to cellular signaling alterations and stress. It is clear that in divergent species, there exists robust organization of nascent rRNA processing events during transcription elongation. This review evaluates the current state of our understanding of the complex relationship between transcription elongation and rRNA processing.
| S-EPMC6744312 | biostudies-literature
Project description:BackgroundIn many animals, the first few hours of life proceed with little or no transcription, and developmental regulation at these early stages is dependent on maternal cytoplasm rather than the zygotic nucleus. Translational control is critical for early Drosophila embryogenesis and is exerted mainly at the gene level. To understand post-transcriptional regulation during Drosophila early embryonic development, we used sucrose polysomal gradient analyses and GeneChip analysis to illustrate the translation profile of individual mRNAs.ResultsWe determined ribosomal density and ribosomal occupancy of over 10,000 transcripts during the first ten hours after egg laying.ConclusionWe report the extent and general nature of gene regulation at the translational level during early Drosophila embryogenesis on a genome-wide basis. The diversity of the translation profiles indicates multiple mechanisms modulating transcript-specific translation. Cluster analyses suggest that the genes involved in some biological processes are co-regulated at the translational level at certain developmental stages.
| S-EPMC1896012 | biostudies-literature
Project description:Dysfunctions in ribosome biogenesis cause developmental defects and increased cancer susceptibility; however, the connection between ribosome assembly and tumorigenesis remains unestablished. Here we show that hCINAP (also named AK6) is required for human 18S rRNA processing and 40S subunit assembly. Homozygous CINAP(-/-) mice show embryonic lethality. The heterozygotes are viable and show defects in 18S rRNA processing, whereas no delayed cell growth is observed. However, during rapid growth, CINAP haploinsufficiency impairs protein synthesis. Consistently, hCINAP depletion in fast-growing cancer cells inhibits ribosome assembly and abolishes tumorigenesis. These data demonstrate that hCINAP reduction is a specific rate-limiting controller during rapid growth. Notably, hCINAP is highly expressed in cancers and correlated with a worse prognosis. Genome-wide polysome profiling shows that hCINAP selectively modulates cancer-associated translatome to promote malignancy. Our results connect the role of hCINAP in ribosome assembly with tumorigenesis. Modulation of hCINAP expression may be a promising target for cancer therapy.
| S-EPMC4974663 | biostudies-literature
Project description:Pre-rRNA synthesis and processing are key steps in ribosome biogenesis. Although recent evidence in yeast suggests that these two processes are coupled, the nature of their association is unclear. In this report, we analyze the coordination between rDNA transcription and pre-rRNA processing in mammalian cells. We found that pol I transcription factor UBF interacts with pre-rRNA processing factors as analyzed by immunoprecipitations, and the association depends on active rRNA synthesis. In addition, injections of plasmids containing the human rDNA promoter and varying lengths of 18S rDNA into HeLa nuclei show that pol I transcription machinery can be recruited to rDNA promoters regardless of the product that is transcribed, whereas subgroups of pre-rRNA processing factors are recruited to plasmids only when specific pre-rRNA fragments are produced. Our observations suggest a model for sequential recruitment of pol I transcription factors and pre-rRNA processing factors to elongating pre-rRNA on an as-needed basis rather than corecruitment to sites of active transcription.
| S-EPMC1783775 | biostudies-literature
Project description:BackgroundIn eukaryotic cells, DNA polymerase delta (Poldelta), whose catalytic subunit p125 is encoded in the Pold1 gene, plays a central role in chromosomal DNA replication, repair, and recombination. However, the physiological role of the Poldelta in mammalian development has not been thoroughly investigated.Methodology/principal findingsTo examine this role, we used a gene targeting strategy to generate two kinds of Pold1 mutant mice: Poldelta-null (Pold1(-/-)) mice and D400A exchanged Poldelta (Pold1(exo/exo)) mice. The D400A exchange caused deficient 3'-5' exonuclease activity in the Poldelta protein. In Poldelta-null mice, heterozygous mice developed normally despite a reduction in Pold1 protein quantity. In contrast, homozygous Pold1(-/-) mice suffered from peri-implantation lethality. Although Pold1(-/-) blastocysts appeared normal, their in vitro culture showed defects in outgrowth proliferation and DNA synthesis and frequent spontaneous apoptosis, indicating Poldelta participates in DNA replication during mouse embryogenesis. In Pold1(exo/exo) mice, although heterozygous Pold1(exo/+) mice were normal and healthy, Pold1(exo/exo) and Pold1(exo/-) mice suffered from tumorigenesis.ConclusionsThese results clearly demonstrate that DNA polymerase delta is essential for mammalian early embryogenesis and that the 3'-5' exonuclease activity of DNA polymerase delta is dispensable for normal development but necessary to suppress tumorigenesis.
| S-EPMC2615215 | biostudies-literature
Project description:Embryonic genome activation (EGA) is a critical event for the preimplantation embryo, which is manifested by changes in chromatin structure, transcriptional machinery, expression of embryonic genes, and degradation of maternal transcripts. The objectives of this study were to determine transcript abundance of HMGN3a and SMARCAL1 in mature bovine oocytes and early bovine embryos, to perform comparative functional genomics analysis of these genes across mammals.New annotations of both HMGN3a and SMARCAL1 were submitted to the Bovine Genome Annotation Submission Database at BovineGenome.org. Careful analysis of the bovine SMARCAL1 consensus gene set for this protein (GLEAN_20241) showed that the NCBI protein contains sequencing errors, and that the actual bovine protein has a high degree of homology to the human protein. Our results showed that there was a high degree of structural conservation of HMGN3a and SMARCAL1 in the mammalian species studied. HMGN3a transcripts were present at similar levels in bovine matured oocytes and 2-4-cell embryos but at higher levels in 8-16-cell embryos, morulae and blastocysts. On the other hand, transcript levels of SMARCAL1 decreased throughout preimplantation development.The high levels of structural conservation of these proteins highlight the importance of chromatin remodeling in the regulation of gene expression, particularly during early mammalian embryonic development. The greater similarities of human and bovine HMGN3a and SMARCAL1 proteins may suggest the cow as a valuable model to study chromatin remodeling at the onset of mammalian development. Understanding the roles of chromatin remodeling proteins during embryonic development emphasizes the importance of epigenetics and could shed light on the underlying mechanisms of early mammalian development.
| S-EPMC2684548 | biostudies-literature