Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene

<p>Abstract</p> <p>Background</p> <p>The peptide hormone ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, gut motility and proliferation of cancer cells. We previously identified a gene on the opposite strand of the ghrelin gene, ghrelinOS (<it>GHRLOS</it>), which spans the promoter and untranslated regions of the ghrelin gene (<it>GHRL</it>). Here we further characterise <it>GHRLOS</it>.</p> <p>Results</p> <p>We have described <it>GHRLOS </it>mRNA isoforms that extend over 1.4 kb of the promoter region and 106 nucleotides of exon 4 of the ghrelin gene, <it>GHRL</it>. These <it>GHRLOS </it>transcripts initiate 4.8 kb downstream of the terminal exon 4 of <it>GHRL </it>and are present in the 3' untranslated exon of the adjacent gene <it>TATDN2 </it>(TatD DNase domain containing 2). Interestingly, we have also identified a putative non-coding <it>TATDN2-GHRLOS </it>chimaeric transcript, indicating that <it>GHRLOS </it>RNA biogenesis is extremely complex. Moreover, we have discovered that the 3' region of <it>GHRLOS </it>is also antisense, in a tail-to-tail fashion to a novel terminal exon of the neighbouring <it>SEC13 </it>gene, which is important in protein transport. Sequence analyses revealed that <it>GHRLOS </it>is riddled with stop codons, and that there is little nucleotide and amino-acid sequence conservation of the <it>GHRLOS </it>gene between vertebrates. The gene spans 44 kb on 3p25.3, is extensively spliced and harbours multiple variable exons. We have also investigated the expression of <it>GHRLOS </it>and found evidence of differential tissue expression. It is highly expressed in tissues which are emerging as major sites of non-coding RNA expression (the thymus, brain, and testis), as well as in the ovary and uterus. In contrast, very low levels were found in the stomach where sense, <it>GHRL </it>derived RNAs are highly expressed.</p> <p>Conclusion</p> <p><it>GHRLOS </it>RNA transcripts display several distinctive features of non-coding (ncRNA) genes, including 5' capping, polyadenylation, extensive splicing and short open reading frames. The gene is also non-conserved, with differential and tissue-restricted expression. The overlapping genomic arrangement of <it>GHRLOS </it>with the ghrelin gene indicates that it is likely to have interesting regulatory and functional roles in the ghrelin axis.</p

The proximal first exon architecture of the murine ghrelin gene is highly similar to its human orthologue

BACKGROUND: The murine ghrelin gene (Ghrl), originally sequenced from stomach tissue, contains five exons and a single transcription start site in a short, 19 bp first exon (exon 0). We recently isolated several novel first exons of the human ghrelin gene and found evidence of a complex transcriptional repertoire. In this report, we examined the 5' exons of the murine ghrelin orthologue in a range of tissues using 5' RACE. -----FINDINGS: 5' RACE revealed two transcription start sites (TSSs) in exon 0 and four TSSs in intron 0, which correspond to 5' extensions of exon 1. Using quantitative, real-time RT-PCR (qRT-PCR), we demonstrated that extended exon 1 containing Ghrl transcripts are largely confined to the spleen, adrenal gland, stomach, and skin. -----CONCLUSION: We demonstrate that multiple transcription start sites are present in exon 0 and an extended exon 1 of the murine ghrelin gene, similar to the proximal first exon organisation of its human orthologue. The identification of several transcription start sites in intron 0 of mouse ghrelin (resulting in an extension of exon 1) raises the possibility that developmental-, cell- and tissue-specific Ghrl mRNA species are created by employing alternative promoters and further studies of the murine ghrelin gene are warranted

Impact Of Two-Stage Weaning On Calf Growth, Behavior, and Vocalizations

https://scholarworks.moreheadstate.edu/student_scholarship_posters/1174/thumbnail.jp

Global perspectives on observing ocean boundary current systems

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Todd, R. E., Chavez, F. P., Clayton, S., Cravatte, S., Goes, M., Greco, M., Ling, X., Sprintall, J., Zilberman, N., V., Archer, M., Aristegui, J., Balmaseda, M., Bane, J. M., Baringer, M. O., Barth, J. A., Beal, L. M., Brandt, P., Calil, P. H. R., Campos, E., Centurioni, L. R., Chidichimo, M. P., Cirano, M., Cronin, M. F., Curchitser, E. N., Davis, R. E., Dengler, M., deYoung, B., Dong, S., Escribano, R., Fassbender, A. J., Fawcett, S. E., Feng, M., Goni, G. J., Gray, A. R., Gutierrez, D., Hebert, D., Hummels, R., Ito, S., Krug, M., Lacan, F., Laurindo, L., Lazar, A., Lee, C. M., Lengaigne, M., Levine, N. M., Middleton, J., Montes, I., Muglia, M., Nagai, T., Palevsky, H., I., Palter, J. B., Phillips, H. E., Piola, A., Plueddemann, A. J., Qiu, B., Rodrigues, R. R., Roughan, M., Rudnick, D. L., Rykaczewski, R. R., Saraceno, M., Seim, H., Sen Gupta, A., Shannon, L., Sloyan, B. M., Sutton, A. J., Thompson, L., van der Plas, A. K., Volkov, D., Wilkin, J., Zhang, D., & Zhang, L. Global perspectives on observing ocean boundary current systems. Frontiers in Marine Science, 6, (2010); 423, doi: 10.3389/fmars.2019.00423.Ocean boundary current systems are key components of the climate system, are home to highly productive ecosystems, and have numerous societal impacts. Establishment of a global network of boundary current observing systems is a critical part of ongoing development of the Global Ocean Observing System. The characteristics of boundary current systems are reviewed, focusing on scientific and societal motivations for sustained observing. Techniques currently used to observe boundary current systems are reviewed, followed by a census of the current state of boundary current observing systems globally. The next steps in the development of boundary current observing systems are considered, leading to several specific recommendations.RT was supported by The Andrew W. Mellon Foundation Endowed Fund for Innovative Research at WHOI. FC was supported by the David and Lucile Packard Foundation. MGo was funded by NSF and NOAA/AOML. XL was funded by China’s National Key Research and Development Projects (2016YFA0601803), the National Natural Science Foundation of China (41490641, 41521091, and U1606402), and the Qingdao National Laboratory for Marine Science and Technology (2017ASKJ01). JS was supported by NOAA’s Global Ocean Monitoring and Observing Program (Award NA15OAR4320071). DZ was partially funded by the Joint Institute for the Study of the Atmosphere and Ocean (JISAO) under NOAA Cooperative Agreement NA15OAR4320063. BS was supported by IMOS and CSIRO’s Decadal Climate Forecasting Project. We gratefully acknowledge the wide range of funding sources from many nations that have enabled the observations and analyses reviewed here

Turtle ghrelin [Correspondence]

In a recent paper, Wang and colleagues described the genomes of two turtles, the Chinese soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas)1. A salient finding was an apparent absence of GHRL, the gene encoding the only known circulating orexigen, the peptide hormone ghrelin. The highly conserved GHRL encodes at least two bioactive peptide hormones, ghrelin2 and obestatin3, which are recognized to have a diverse range of functions in a number of cell types and physiological systems4, 5. Wang and colleagues hypothesized that the absence of ghrelin was associated with the low metabolic rate observed in these turtle species1

The mitochondrial genome of the black-tailed dusky antechinus (Antechinus arktos)

In this study, we report the mitochondrial genome of the black-tailed antechinus (Antechinus arktos), a recently-discovered, endangered carnivorous marsupial inhabiting a caldera that straddles the border of Australia’s mid-east coast. The circular A. arktos genome is 17,334 bp in length and has an AT content of 63.3%. Its gene content and arrangement are consistent with reported marsupial mitogenome assemblies.</p

Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Hyperinsulinaemia, obesity and dyslipidaemia are independent and collective risk factors for many cancers. Here, the long-term effects of a 23% Western high-fat diet (HFD) in two immunodeficient mouse strains (NOD/SCID and Rag1-/-) suitable for engraftment with human-derived tissue xenografts, and the effect of diet-induced hyperinsulinaemia on human prostate cancer cell line xenograft growth, were investigated. Rag1(-/-) and NOD/SCID HFD-fed mice demonstrated diet-induced impairments in glucose tolerance at 16 and 23 weeks post weaning. Rag1(-/-) mice developed significantly higher fasting insulin levels (2.16 +/- 1.01 ng/ml, P = 0.01) and increased insulin resistance (6.70 +/- 1.68 HOMA-IR, P = 0.01) compared to low-fat chow-fed mice (0.71 +/- 0.12 ng/ml and 2.91 +/- 0.42 HOMA-IR). This was not observed in the NOD/SCID strain. Hepatic steatosis was more extensive in Rag1(-/-) HFD-fed mice compared to NOD/SCID mice. Intramyocellular lipid storage was increased in Rag1(-/-) HFD-fed mice, but not in NOD/SCID mice. In Rag1(-/-) HFD-fed mice, LNCaP xenograft tumours grew more rapidly compared to low-fat chow-fed mice. This is the first characterisation of the metabolic effects of longterm Western HFD in two mouse strains suitable for xenograft studies. We conclude that Rag1(-/-) mice are an appropriate and novel xenograft model for studying the relationship between cancer and hyperinsulinaemia

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

Background: Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified