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991.
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Background
Identifying the endogenous RNA induced silencing complex(RISC)-associated RNAs is essential for understanding the cellular regulatory networks by miRNAs. Recently, isolation of RISC-associated mRNAs using antibody was reported, but their method needs a large amount of initial materials. We tried to improve the protocol and constructed an efficient and convenient system for analyzing miRNA and mRNA contents in RISC.Findings
With our protocol, it is possible to clone both miRNAs and mRNAs from the endogenous RISC-associated RNAs immunoprecipitated from less than 107 cells, and we show the ability of our system to isolate the particular target mRNAs for a specific miRNA from the RISC-associated mRNAs using well-characterized miR-122 as an example. After introduction of miR-122 into HepG2 cells, we found several cDNA clones that have miR-122 target sequences. Four of these clones that were concentrated in RISC but decreased in total RNA fraction are expected to be miR-122 target candidates. Interestingly, we found substantial amounts of Alu-related sequences, including both free Alu RNA and Alu-embedded mRNA, which might be one of the general targets for miRNA, in the cDNA clones from the RISC-associated mRNAs.Conclusion
Our method thus enables us to examine not only dynamic changes in miRNA and mRNA contents in RISC but also the relationship of miRNA and target mRNA. We believe that our method can contribute to understanding cellular regulatory networks by miRNAs. 相似文献994.
Akinori Yamasaki Shekar Menon Sidney Yu Jemima Barrowman Timo Meerloo Viola Oorschot Judith Klumperman Ayano Satoh Susan Ferro-Novick 《Molecular biology of the cell》2009,20(19):4205-4215
The GTPase Rab1 regulates endoplasmic reticulum-Golgi and early Golgi traffic. The guanine nucleotide exchange factor (GEF) or factors that activate Rab1 at these stages of the secretory pathway are currently unknown. Trs130p is a subunit of the yeast TRAPPII (transport protein particle II) complex, a multisubunit tethering complex that is a GEF for the Rab1 homologue Ypt1p. Here, we show that mammalian Trs130 (mTrs130) is a component of an analogous TRAPP complex in mammalian cells, and we describe for the first time the role that this complex plays in membrane traffic. mTRAPPII is enriched on COPI (Coat Protein I)-coated vesicles and buds, but not Golgi cisternae, and it specifically activates Rab1. In addition, we find that mTRAPPII binds to γ1COP, a COPI coat adaptor subunit. The depletion of mTrs130 by short hairpin RNA leads to an increase of vesicles in the vicinity of the Golgi and the accumulation of cargo in an early Golgi compartment. We propose that mTRAPPII is a Rab1 GEF that tethers COPI-coated vesicles to early Golgi membranes. 相似文献
995.
Ramkumar Menon Brad Pearce Digna R Velez Mario Merialdi Scott M Williams Stephen J Fortunato Poul Thorsen 《Reproductive biology and endocrinology : RB&E》2009,7(1):62
Objective
To study pathophysiologic pathways in spontaneous preterm birth and possibly the racial disparity associating with maternal and fetal genetic variations, using bioinformatics tools. 相似文献996.
Cornish J Callon KE Mountjoy KG Bava U Lin JM Myers DE Naot D Reid IR 《American journal of physiology. Endocrinology and metabolism》2003,284(6):E1181-E1190
alpha-Melanocyte-stimulating hormone (alpha-MSH), a 13-amino acid peptide produced in the brain and pituitary gland, is a regulator of appetite and body weight, and its production is regulated by leptin, a factor that affects bone mass when administered centrally. alpha-MSH acts via melanocortin receptors. Humans deficient in melanocortin receptor 4 (MC4-R) have increased bone mass, and MC4-R has been identified in an osteoblast-like cell line. Thus alpha-MSH may act directly on the skeleton, a question addressed by the present studies. In primary cultures of osteoblasts and chondrocytes, alpha-MSH dose dependently (>or=10(-9) M) stimulated cell proliferation. In bone marrow cultures, alpha-MSH (>10(-9) M) stimulated osteoclastogenesis. Systemic administration of alpha-MSH to mice (20 injections of 4.5 microg/day) decreased the trabecular bone volume in the proximal tibiae from 19.5 +/- 1.8 to 15.2 +/- 1.4% (P = 0.03) and reduced trabecular number (P = 0.001). Radiographic indexes of trabecular bone, assessed by phase-contrast X-ray imaging, confirmed the bone loss. It is concluded that alpha-MSH acts directly on bone, increasing bone turnover, and, when administered systemically, it decreases bone volume. The latter result may also be contributed to by alpha-MSH effects elsewhere, such as the adipocyte, pancreatic beta-cell, or central nervous system. 相似文献
997.
The elucidation of the role of highly conserved polar amino acids in the transmembrane helices of G-protein-coupled receptors (GPCRs) is important in understanding the mechanism of receptor activation. To this end, the significance of a highly conserved serine residue in the third transmembrane alpha-helix (TM3) of the luteinizing hormone/human chorionic gonadotropin receptor (LH/hCGR) in regulating receptor activation was examined. Results showed that mutation of serine 431 to alanine (S431A) decreased the ability of the receptor to mediate cAMP production in response to hCG, suggesting that S431 stabilizes the active state of the receptor. Homology with other GPCRs suggests that S431 may participate in the coordination of a Na(+) ion. Since Na(+) has been found to stabilize the active state of the receptor in the presence of hCG, the possibility that S431 promotes receptor activation by mediating the effects of Na(+) was explored. Results showed that the regulation of hormone-induced receptor activation by S431 was independent of Na(+). A rhodopsin-based homology model of the TM region of the LH/hCGR was developed to identify other amino acids that might mediate the effects of Na(+) on receptor function. Results indicate that substitution of an Asp at position 556 with Tyr alters the ability of Na(+) to regulate receptor activation. The homology model is used to explain this result as well as to identify a mechanism through which S431 may regulate receptor signaling. Taken together, these studies provide novel insights into the mechanism of LH/hCG receptor activation. 相似文献
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beta1 integrins expression in adult rat ventricular myocytes and its role in the regulation of beta-adrenergic receptor-stimulated apoptosis 总被引:3,自引:0,他引:3
Communal C Singh M Menon B Xie Z Colucci WS Singh K 《Journal of cellular biochemistry》2003,89(2):381-388
We have shown that the stimulation of beta-adrenergic receptors (beta-AR) increases apoptosis in adult rat ventricular myocytes (ARVMs). Integrins, a family of alphabeta-heterodimeric cell surface receptors, are postulated to play a role in ventricular remodeling. Here, we show that norepinephrine (NE) increases beta1 integrins expression in ARVMs via the stimulation of alpha1-AR, not beta-AR. Inhibition of ERK1/2 using PD 98059, an inhibitor of ERK1/2 pathway, inhibited alpha1-AR-stimulated increases in beta1 integrins expression. Activation of beta1 integrins signaling pathway using laminin (LN) inhibited beta-AR-stimulated apoptosis as measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-staining and flow cytometry. Likewise, ligation of beta1 integrins with anti-beta1 integrin antibodies prevented beta-AR-stimulated apoptosis. Treatment of cells using LN or anti-beta1 integrin antibodies activated ERK1/2 pathway. PD 98059 inhibited activation of ERK1/2 by LN, and prevented the anti-apoptotic effects of LN. Thus (1) stimulation of alpha1-AR regulates beta1 integrins expression via the activation of ERK1/2, (2) beta1 integrins signaling protects ARVMs from beta-AR-stimulated apoptosis, (3) activation of ERK1/2 plays a critical role in the anti-apoptotic effects of beta1-integrin signaling. These data suggest that beta1 integrin signaling protects ARVMs against beta-AR-stimulated apoptosis possibly via the involvement of ERK1/2. 相似文献