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Numerous cytokines, receptors, and ectoenzymes, including angiotensin I-converting enzyme (ACE), are shed from the cell surface by limited proteolysis at the juxtamembrane stalk region. The membrane-proximal C domain of ACE has been implicated in sheddase-substrate recognition. We mapped the functional boundaries of the testis ACE ectodomain (identical to the C domain of somatic ACE) by progressive deletions from the N- and C-termini and analysing the effects on catalytic activity, stability, and shedding in transfected cells. We found that deletions extending beyond Leu37 at the N-terminus and Trp616 at the C-terminus abolished catalytic activity and shedding, either by disturbing the ectodomain conformation or by inhibiting maturation and surface expression. Based on these data and on sequence alignments, we propose that the boundaries of the ACE ectodomain are Asp40 at the N-terminus and Gly615 at the C-terminus.
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http://dx.doi.org/10.1016/s0006-291x(02)02324-0 | DOI Listing |
Mol Cell
November 2024
Department of Clinical Laboratory, The First Affiliated Hospital of USTC, The RNA Institute, School of Basic Medical Sciences, Division of Life Science and Medicine, University of Science and Technology of China (USTC), Hefei 230027, China. Electronic address:
Circular RNAs (circRNAs) are natural outputs of eukaryotic transcription and RNA processing and have emerged as critical regulators in physiology and diseases. Although multiple cis-elements and trans-factors are reported to modulate the backsplicing of circRNA biogenesis, most of these regulations play roles in flanking introns of circRNAs. Here, using a genome-wide CRISPR knockout screen, we have identified an evolutionarily conserved RNA-binding protein ZC3H14 in regulating circRNA biogenesis.
View Article and Find Full Text PDFZhonghua Nan Ke Xue
March 2024
Department of Andrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China..
Zhonghua Nan Ke Xue
February 2024
Center of Reproductive Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010000, China.
Objective: To investigate the effect of miR-199b-5p knockout on the expression of the CREM gene in the semen and testis of mice.
Methods: We selected 8 miR-199b-5p knockout (KO) male mice (the KO group) and another 8 wild-type (WT) C57BL/6 male mice (the WT group), and observed the changes in their body weight, testicular index, testis structure and sperm morphology. We detected sperm concentration under the microscope, determined the mRNA and protein expression levels of CREM in the semen and testis by RT-qPCR and Western blot respectively, and predicted the targeting relationship between CREM and miR-199b-5p using the online database.
Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored.
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