Parathyroid hormone (PTH) mRNA levels are posttranscriptionally increased by hypocalcemia and decreased by hypophosphatemia, and this is mediated by cytosolic proteins binding to the PTH mRNA 3-untranslated region (UTR). The same proteins are also present in other tissues, such as brain, but only in the parathyroid is their binding regulated by calcium and phosphate. The function of the PTH mRNA 3-UTR-binding proteins was studied using an in vitro degradation assay. Competition for the parathyroid-binding proteins by excess unlabeled 3-UTR destabilized the full-length PTH transcript in this assay, indicating that these proteins protect the RNA from RNase activity. The PTH RNA 3-UTR-binding proteins were purified by RNA affinity chromatography of rat brain S-100 extracts. The eluate from the column was enriched in PTH RNA 3-UTR binding activity. Addition of eluate to the in vitro degradation assay with parathyroid protein extracts stabilized the PTH transcript. A major band from the eluate at 50 kDa was sequenced and was identical to AU-rich binding protein (AUF1). Recombinant AUF1 bound the full-length PTH mRNA and the 3-UTR. Added recombinant AUF1 also stabilized the PTH transcript in the in vitro degradation assay. Our results show that AUF1 is a protein that binds to the PTH mRNA 3-UTR and stabilizes the PTH transcript.Serum calcium is maintained within a narrow physiological range mainly due to the action of PTH, 1 which acts together with the biologically active metabolite of vitamin D, 1␣,25-dihydroxyvitamin D (1). A seven-transmembranous calciumsensing receptor on the parathyroid (PT) cell recognizes small changes in serum ionized calcium to regulate PTH secretion (2). Low serum calcium increases not only PTH secretion, but also PTH mRNA levels (3) and, if prolonged, PT cell proliferation (4). PTH then acts to correct serum calcium by mobilizing calcium from bone and renal reabsorption of calcium. Phosphate also regulates the PT, with low serum phosphate decreasing serum PTH, PTH mRNA levels, and parathyroid cell proliferation (5-8). Patients with chronic renal failure are unable to excrete the large amounts of phosphorus in the diet. They develop severe complications due to high serum phosphate, including hyperparathyroidism with overactivity of the PT gland, bone pain, and increased mortality (9). There is therefore great interest in understanding the regulation of the PT by calcium and phosphate.PTH gene expression is markedly increased by hypocalcemia and decreased by hypophosphatemia, and these effects in vivo are post-transcriptional (5, 10). The PTH cDNA consists of three exons coding for the 5Ј-UTR (exon I), the prepro region of PTH (exon II), and the structural hormone together with the 3Ј-UTR (exon III) (11, 12). The rat 3Ј-UTR is 239 nt long out of the 712 nt of the full-length PTH RNA (12). We have shown that cytosolic proteins from parathyroids bind to the 3Ј-UTR of the rat PTH mRNA and regulate mRNA stability (10). PT proteins from hypocalcemic rats show increased binding to the PTH mRNA 3Ј-...

Investigation of SARS-CoV-2 spread and identification of variants in sewers has been demonstrated to accurately detect prevalence of viral strains and is advantageous to clinical sampling in population catchment size. Herein, we utilized an established nationwide system of wastewater sampling and viral concentration approaches to perform large-scale surveillance of SARS-CoV-2 variants in nine different locations across Israel that were sampled from August 2020 to February 2021 and sequenced (n=58). Viral sequences obtained from the wastewater samples had high coverages of the genome, and mutation analyses successfully identified the penetration of the B.1.1.7 variant into Israel in December 2020 in the central and north regions, and its spread into additional regions in January and February 2021, corresponding with clinical sampling results. Moreover, the wastewater analysis identified the B.1.1.7 variant in December 2020 in regions in which non-sufficient clinical sampling was available. Other variants of concern examined, including P.1 (Brazil/Manaus), B.1.429 (USA/California), B.1.526 (USA/New York), A.23.1 (Uganda) and B.1.525 (Unknown origin), did not show consistently elevated frequencies. This study exemplifies that surveillance by sewage is a robust approach which allows to monitor the diversity of SARS-CoV-2 strains circulating in the community. Most importantly, this approach can pre-identify the emergence of epidemiologically or clinically relevant mutations/variants, aiding in public health decision making.

HIV type 1 (HIV-1) was shown to assemble either at the plasma membrane or in the membrane of late endosomes. Now, we report an essential role for human ubiquitin ligase POSH (Plenty of SH3s; hPOSH), a trans-Golgi network-associated protein, in the targeting of HIV-1 to the plasma membrane. Small inhibitory RNA-mediated silencing of hPOSH ablates virus secretion and Gag plasma membrane localization. Reintroduction of native, but not a RING finger mutant, hPOSH restores virus release and Gag plasma membrane localization in hPOSH-depleted cells. Furthermore, expression of the RING finger mutant hPOSH inhibits virus release and induces accumulation of intracellular Gag in normal cells. Together, our results identify a previously undescribed step in HIV biogenesis and suggest a direct function for hPOSH-mediated ubiquitination in protein sorting at the trans-Golgi network. Consequently, hPOSH may be a useful host target for therapeutic intervention.protein sorting͞trafficking ͉ ubiquitin conjugation ͉ ubiquitin ligase ͉ HIV assembly ͉ HIV secretion

Regulation of the parathyroid hormone gene by vitamin D,late the PTH gene and these will be considered in the calcium, and phosphate. Secondary hyperparathyroidism is a present review. frequent complication of chronic renal failure resulting in severe bone disease. Secondary hyperparathyroidism is composed of increased in parathyroid hormone (PTH) synthesis THE PTH GENEand secretion due to an increase in PTH gene expression andThe parathyroid cell is committed to the synthesis of parathyroid cell proliferation. PTH gene expression is regulated by calcium, phosphate and 1,25-dihydroxy vitamin D PTH, implying that there are specific trans-and cis-fac-(1,25(OH) 2 D). 1,25(OH) 2 D 3 injected to rats leads to a dramatic tors acting on the PTH gene that are specific to the cell decrease in PTH gene transcription without any increase in and gene. The gene itself is expressed once in the human serum calcium. Hypocalcemia leads to a large increase in PTH genome and is a relatively simple gene. It has been cloned mRNA levels which is post-transcriptional. Hypophosphatein a number of species and in all species it consists of mia leads to a marked decrease in PTH gene expression that is also post-transcriptional. The mechanisms of the post-tran-three exons and two introns. These exons code for the scriptional effects of calcium and phosphate on the PTH gene 5Ј-untranslated region and the presequence of the gene, have shown to be due to changes in protein-RNA interactions the pro-sequence and for the translated hormone and at the PTH mRNA 3Ј-UTR. Hypocalcemia leads to increased the 3Ј-untranslated region, respectively. The PTH gene binding of parathyroid cytosolic proteins to the PTH mRNA 1 C.Y. was on sabbatical leave from Erciyes University Medical School, cium [3]. There is a subsequent decrease in PTH secretion. Kayseri, Turkey.