Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian testis contains high levels of a protein, L-isoaspartyl (D-aspartyl) O-methyltransferase (PIMT), postulated to play a role in the repair of age-damaged proteins. To examine the regulation of PIMT concentrations during the development of spermatozoa, poly(A)+ RNA was isolated from purified populations of pachytene spermatocytes and round spermatids. Northern blot analysis revealed that a unique 1.1-1.3 kb PIMT transcript is present in preparations of round spermatid and pachytene spermatocyte poly (A)+ RNA. The concentration of this small PIMT transcript is at least four times higher in mRNA isolated from round spermatids than in mRNA isolated from pachytene spermatocytes, indicating that the PIMT gene is actively transcribed during the haploid phase of spermatogenesis. The germ cell-specific PIMT transcripts are distributed between the polysomal fraction and the nonpolysomal fractions of testis RNA, suggesting that translational controls also contribute to the high concentrations of PIMT in mammalian sperm. PIMT function is not essential for spermatogenesis because the testes from transgenic mice lacking PIMT activity have normal levels of protamine transcripts, and because functional sperm can be recovered from the cauda epididymis. The protein repair function of the PIMT may be more important in maintaining the fertilization competence of translationally-inactive mature sperm during the prolonged period of epididymal transit and storage in the male reproductive tract.
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PMID:Translation of a unique transcript for protein isoaspartyl methyltransferase in haploid spermatids: implications for protein storage and repair. 1081 44

While the risks of maternal alcohol abuse during pregnancy are well-established, several preclinical studies suggest that chronic preconception alcohol consumption by either parent may also have significance consequences for offspring health and development. Notably, since isogenic male mice used in these studies are not involved in gestation or rearing of offspring, the cross-generational effects of paternal alcohol exposure suggest a germline-based epigenetic mechanism. Many recent studies have demonstrated that the effects of paternal environmental exposures such as stress or malnutrition can be transmitted to the next generation via alterations to small noncoding RNAs in sperm. Therefore, we used high throughput sequencing to examine the effect of preconception ethanol on small noncoding RNAs in sperm. We found that chronic intermittent ethanol exposure altered several small noncoding RNAs from three of the major small RNA classes in sperm, tRNA-derived small RNA (tDR), mitochondrial small RNA, and microRNA. Six of the ethanol-responsive small noncoding RNAs were evaluated with RT-qPCR on a separate cohort of mice and five of the six were confirmed to be altered by chronic ethanol exposure, supporting the validity of the sequencing results. In addition to altered sperm RNA abundance, chronic ethanol exposure affected post-transcriptional modifications to sperm small noncoding RNAs, increasing two nucleoside modifications previously identified in mitochondrial tRNA. Furthermore, we found that chronic ethanol reduced epididymal expression of a tRNA methyltransferase, Nsun2, known to directly regulate tDR biogenesis. Finally, ethanol-responsive sperm tDR are similarly altered in extracellular vesicles of the epididymis (i.e., epididymosomes), supporting the hypothesis that alterations to sperm tDR emerge in the epididymis and that epididymosomes are the primary source of small noncoding RNAs in sperm. These results add chronic ethanol to the growing list of paternal exposures that can affect small noncoding RNA abundance and nucleoside modifications in sperm. As small noncoding RNAs in sperm have been shown to causally induce heritable phenotypes in offspring, additional research is warranted to understand the potential effects of ethanol-responsive sperm small noncoding RNAs on offspring health and development.
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PMID:Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes. 2947 46