The Ribb-osome: Ribbon boosts ribosomal protein gene expression to coordinate organ form and function

Cell growth is well defined for the late (post-embryonic) stages of development, but evidence for early (embryonic) cell growth during post-mitotic morphogenesis is quite limited. Here, we identify early cell growth as a key characteristic of tubulogenesis in the Drosophila embryonic salivary gland (SG). A BTB/POZ domain nuclear factor, Ribbon (Rib), mediates this early cell growth. Rib binds the transcription start site of nearly every SG-expressed ribosomal protein gene (RPG) and is required for full expression of all RPGs tested. Rib binding to RPG promoters in vitro is weak and not sequence-specific, suggesting that specificity is achieved through cofactor interactions. Consistent with this hypothesis, we demonstrate the ability of Rib to physically interact with each of the three known contributors to RPG transcription. Surprisingly, Rib-dependent early cell growth in another tubular organ, the embryonic trachea, is not mediated by direct RPG transcription. These findings support a model of early cell growth sustained by transcriptional regulatory networks customized for organ form and function.

Dried seahorse in traditional medicine: A narrative review

Seahorses are classified as members of Syngnathidae family, which includes pipefishes, pipehorses, and seadragons. China, including Hong Kong, uses 250 tons of seahorses as Traditional Chinese Medicine (TCM) every year. It is popular in Traditional Medicines (TM) especially TMC and its derivatives. The TCM formulations of dried seahorse strengthens the kidney and enhances immunity to treat the aging process. Base on the molecular biology analysis, S6 ribosomal protein gene, S7 ribosomal protein gene, and the S20 ribosomal protein gene have been identified in dried seahorses, which help to reduce the cough symptoms. The present mini-review discusses the background of the use of dried seahorses, the TCM theory, the TCM formulations, the molecular biology, and analysis of its usage in traditional medicine.

Gds1 interacts with NuA4 to promote H4 acetylation at ribosomal protein genes

In our previously published studies, RNA polymerase II transcription initiation complexes were assembled from yeast nuclear extracts onto immobilized transcription templates and analyzed by quantitative mass spectrometry. In addition to the expected basal factors and coactivators, we discovered that the uncharacterized protein Gds1 showed activator- stimulated association with promoter DNA. Gds1 co-precipitated with the histone H4 acetyltransferase NuA4, and its levels often tracked with NuA4 in immobilized template experiments. GDS1 deletion led to reduction in H4 acetylation in vivo and other phenotypes consistent with partial loss of NuA4 activity. Genome-wide chromatin immunoprecipitation revealed that the reduction in H4 acetylation was strongest at ribosomal protein gene promoters and other genes with high NuA4 occupancy. Therefore, while Gds1 is not a stoichiometric subunit of NuA4, we propose that it interacts with and modulates NuA4 in specific promoter contexts. Gds1 has no obvious metazoan homolog, but structural predictions suggest it may be distantly related to the DEK protein.

Yorkie ensures robust tissue growth in Drosophila ribosomal protein mutants

Heterozygosity of a ribosomal protein gene causes a variety of developmental abnormalities in humans, which are collectively known as ribosomopathies, yet the underlying mechanisms remain elusive. Here, we analyzed Drosophila mutants heterozygous for a ribosomal protein gene, called Minute (M)/+ mutants. We found that, while M/+ flies develop essentially normal wings, simultaneous deletion of one copy of the Hippo pathway effector yki resulted in severe wing growth defects. These defects were caused by JNK-mediated cell death in the wing pouch via Eiger/TNF signaling. The JNK activation in M/+, yki/+ wing discs required a caspase Dronc, which is normally blocked by DIAP. Notably, heterozygosity of yki reduced DIAP1 expression in the wing pouch, leading to elevation of Dronc activity. Dronc and JNK formed a positive feedback loop that amplifies Dronc activation, leading to apoptosis. Our observations suggest a novel mechanism of robust tissue growth whereby tissues with reduced ribosomal protein prevent ectopic apoptosis via Yki activity.

Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose

Aneuploidy causes birth defects and miscarriages, occurs in nearly all cancers and is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein (Rp) gene mutations are also eliminated, by cell competition with normal cells. Because Rp genes are spread across the genome, their copy number is a potential marker for aneuploidy. We found that elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. Segmentally aneuploid cells derived from targeted chromosome excisions were eliminated by the RpS12-Xrp1 cell competition pathway if they differed from neighboring cells in Rp gene dose, whereas cells with normal doses of the Rp and eIF2γ genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in Rp gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.

The Pennsylvania grotto sculpin: population genetics

The Pennsylvania grotto sculpin is known from just two caves of the Nippenose Valley in central Pennsylvania, USA. They exhibit emergent troglobitic morphological traits and are the second northern-most cave adapted fish in the world. Two mitochondrial (16S rRNA and D-loop gene) and one nuclear (S7 ribosomal protein gene intron) gene in both cave and epigean populations were sequenced. For the three markers, a large proportion of cave specimens possess unique haplotypes not found in their local surface counterparts, suggesting a vicariance in their evolutionary history. The cave population also has haplotypes from two separate lineages of surface sculpins of the Cottus cognatus/bairdii species complex. Since morphology, nuclear, and mitochondrial markers are not correlated among cave individuals, hybridization with introgression is suggested.

Cell competition removes segmental aneuploid cells from Drosophila imaginal disc-derived tissues based on ribosomal protein gene dose

ABSTRACTAneuploidy causes birth defects and miscarriages, occurs in nearly all cancers, and is a hallmark of aging. Individual aneuploid cells can be eliminated from developing tissues by unknown mechanisms. Cells with ribosomal protein (Rp) gene mutations are also eliminated, by cell competition with normal cells. Because Rp genes are spread across the genome, their copy number is a marker for chromosome aberrations. Elimination of imaginal disc cells with irradiation-induced genome damage often required cell competition genes. When defined chromosome regions were deleted, segmentally-aneuploid cells were eliminated by the RpS12-Xrp1 cell competition pathway in an apoptosis- dependent manner when they differed from neighboring cells in Rp gene dose. Cells with normal doses of the Rp (and eIF2γ) genes survived and differentiated adult tissues. Thus, cell competition, triggered by differences in Rp gene dose between cells, is a significant mechanism for the elimination of aneuploid somatic cells, likely to contribute to preventing cancer.

Epithelial cell-turnover ensures robust coordination of tissue growth in Drosophila ribosomal protein mutants

Highly reproducible tissue development is achieved by robust, time-dependent coordination of cell proliferation and cell death. To study the mechanisms underlying robust tissue growth, we analyzed the developmental process of wing imaginal discs in Drosophila Minute mutants, a series of heterozygous mutants for a ribosomal protein gene. Minute animals show significant developmental delay during the larval period but develop into essentially normal flies, suggesting there exists a mechanism ensuring robust tissue growth during abnormally prolonged developmental time. Surprisingly, we found that both cell death and compensatory cell proliferation were dramatically increased in developing wing pouches of Minute animals. Blocking the cell-turnover by inhibiting cell death resulted in morphological defects, indicating the essential role of cell-turnover in Minute wing morphogenesis. Our analyses showed that Minute wing discs elevate Wg expression and JNK-mediated Dilp8 expression that causes developmental delay, both of which are necessary for the induction of cell-turnover. Furthermore, forced increase in Wg expression together with developmental delay caused by ecdysone depletion induced cell-turnover in the wing pouches of non-Minute animals. Our findings suggest a novel paradigm for robust coordination of tissue growth by cell-turnover, which is induced when developmental time axis is distorted.

H2A.B is a cancer/testis factor involved in activation of ribosome biogenesis in Hodgkin Lymphoma

ABSTRACTTestis-specific regulators of chromatin function are commonly ectopically expressed in human cancers, but their roles are poorly understood. Examination of 81 primary Hodgkin Lymphoma (HL) samples showed that the ectopic expression of the eutherian testis-specific histone variant H2A.B is an inherent feature of HL. In experiments using two HL-derived cell lines derived from different subtypes of HL, H2A.B knockdown inhibited cell proliferation. H2A.B was enriched in both the nucleoli of these HL cell lines and primary HL samples. We found that H2A.B enhanced ribosomal DNA (rDNA) transcription, was enriched at the rDNA promoter and transcribed regions, and interacted with RNA Pol I. Depletion of H2A.B caused the loss of RNA Pol I from rDNA chromatin. Remarkably, H2A.B was also required for high levels of ribosomal protein gene expression being located at the transcriptional start site and within the gene body. H2A.B knockdown reduced gene body chromatin accessibility of active RNA Pol II genes concurrent with a decrease in transcription. Taken together, our data show that in HL H2A.B has acquired a new function, the ability to increase ribosome biogenesis.

Evidence on the paleodrainage connectivity during Pleistocene: Phylogeography of a hypoptopomatine endemic to southeastern Brazilian coastal drainages

The coastal basins of southeastern Brazil are influenced by climatic changes that caused sea-level oscillations during the Pleistocene. These marine transgressions and regressions can generate isolation and connection among coastal rivers. In this region, freshwater fishes are excellent models for phylogeographic studies because their distributions may have been affected by geographical and ecological changes resulting from these processes. Therefore, the main objective of this study was to evaluate the effects of Pleistocene sea-level changes on the genetic structure of the loricariid Hisonotus leucofrenatus throughout its area of occurrence. Two genes were sequenced: Cytochrome Oxidase subunit 1 (mitochondrial gene) and rpS7 ribosomal protein gene intron 1 (nuclear gene) from specimens representing 14 river drainages. The genetic data corroborate a divide for freshwater fish by the Serra do Tabuleiro mountain in Santa Catarina State. This divide determines two main genetic groups in H. leucofrenatus: one group to the south and one to the north of this mountain range. The genetic structure observed coincide with the limits of estimated paleodrainage systems for the region, supporting that marine transgressions and regressions during the Pleistocene influenced the biogeographical history of H. leucofrenatus.