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Notch signaling in spermatogenesis and male (in)fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Mahitha Sahadevan, Pradeep G. Kumar
The DTC of the gonad regulates the mitotic and meiotic divisions in the germ cells through notch signaling with the help of certain ribonucleic acid regulators (like FBF-1, FBF-2, female germline-specific tumor suppressor gld-1 [GLD-1], poly(A) RNA polymerase gld-2 [GLD-2], defective in germ line development protein 3 [GLD-3] and nanOS related [NOS-3]). The proximity of the germ cells to the DTC is the main criteria for switching of the cell division from mitosis to meiosis due to signaling gradients generated among cells through diffusion barriers (21,58,76,86). The whole region of gonads can be divided into three zones based on cell type—mitotic, transition and meiotic zones. A mitotic/progenitor zone (two progenitor zones in case of hermaphrodite at the distal end of gonadal arms and one in the male) is formed of the stem cell niche region, consisting of mitotically dividing cells, which have the capability of both self-renewal as well as production of differentiating gametes (Figure 12.4). DTC expresses protein lag-2 (LAG-2) notch ligand, whereas GLP-1/NOTCH receptor is expressed in the germ cells. The binding of LAG-2 to GLP-1 receptor in the germ cells triggers notch signaling and promotes mitotic division in the cells by inhibiting meiotic regulators. Although glp-1 messenger RNA is present in all germ cells, its protein is expressed only in the germ cells near the distal end. This gradient expression of GLP-1 protein is regulated by a translation repressor called GLD-1, which inhibits the translation of glp-1 mRNA in the meiotic region germ cell by binding to their 3′UTR region (7,53,56,58,59,81,82). In addition to DTC, AC/VU precursor cells also regulate germline proliferation in larval form by the same mechanism, since it also expresses LAG-2 protein (73).
Current progress of miRNA-derivative nucleotide drugs: modifications, delivery systems, applications
Published in Expert Opinion on Drug Delivery, 2022
Charles Asakiya, Liye Zhu, Jieyu Yuhan, Longjiao Zhu, Kunlun Huang, Wentao Xu
3’ modification could improve the stability of mdCNDs. In 2009, Katoh et al. designed a cytoplasmic poly (A) polymerase germline development 2 (GLD-2) (or terminal uridylyltransferase 2 (TUTase 2), which cause 3′ terminal adenylation, which protects miR-122 from degradation, thereby increasing its stability[30]. The results further revealed that a reduction in GLD-2 in liver cells led to the loss of the 23-nucleotide adenylated miR-122 variant but at the same time elongated the 21 nt variant. Therefore, this study indicates that GLD-2 loss of 3’ adenylation leaves miR-122 susceptible to exonuclease degradation. Many short RNAs (including miRNAs in plants and piRNAs in animals) require the Hua enhancer 1 (HEN1)-mediated 2′-O-methylation (2′-OMe) modification at the 3′ end for their stability[31]. Uridylation-mediated 3′-to-5′ truncation and 3′ tailing result in miRNA degradation and heterogeneity at the 3′ end.