共查询到20条相似文献,搜索用时 15 毫秒
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Background
It is generally believed that the miRNA processing machinery ensures the generation of a mature miRNA with a fixed sequence, particularly at its 5′ end. However, we and others have recently noted that the ends of a given mature miRNA are not absolutely fixed, but subject to variation. Neither the significance nor the mechanism behind the generation of such miRNA polymorphism is understood. miR-142 is an abundantly expressed miRNA in hematopoietic cells and exhibits a high frequency of 5′ end polymorphism.Methodology/Principal Findings
Here we show that a shift in the Drosha processing of pri-miRNA generates multiple forms of miR-142s in vivo with differing 5′ ends that might target different genes. Sequence analysis of several pre-miRNA ends cloned from T cells reveals that unlike many other pri-miRNAs that are processed into a single pre-miRNA, pri-miR-142 is processed into 3 distinct pre-miR-142s. Dicer processing studies suggest that each of the 3 pre-miR-142s is processed into a distinct double-stranded miRNA, giving rise to 4 mature miRNA variants that might regulate different target gene pools.Conclusions/Significance
Thus, alternative Drosha processing might be a novel mechanism for diversification of the miRNA target gene pool. 相似文献4.
Wenting Luo Zhe Ji Zhenhua Pan Bei You Mainul Hoque Wencheng Li Samuel I. Gunderson Bin Tian 《PLoS genetics》2013,9(7)
The human gene encoding the cleavage/polyadenylation (C/P) factor CstF-77 contains 21 exons. However, intron 3 (In3) accounts for nearly half of the gene region, and contains a C/P site (pA) with medium strength, leading to short mRNA isoforms with no apparent protein products. This intron contains a weak 5′ splice site (5′SS), opposite to the general trend for large introns in the human genome. Importantly, the intron size and strengths of 5′SS and pA are all highly conserved across vertebrates, and perturbation of these parameters drastically alters intronic C/P. We found that the usage of In3 pA is responsive to the expression level of CstF-77 as well as several other C/P factors, indicating it attenuates the expression of CstF-77 via a negative feedback mechanism. Significantly, intronic C/P of CstF-77 pre-mRNA correlates with global 3′UTR length across cells and tissues. In addition, inhibition of U1 snRNP also leads to regulation of the usage of In3 pA, suggesting that the C/P activity in the cell can be cross-regulated by splicing, leading to coordination between these two processes. Importantly, perturbation of CstF-77 expression leads to widespread alternative cleavage and polyadenylation (APA) and disturbance of cell proliferation and differentiation. Thus, the conserved intronic pA of the CstF-77 gene may function as a sensor for cellular C/P and splicing activities, controlling the homeostasis of CstF-77 and C/P activity and impacting cell proliferation and differentiation. 相似文献
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M. del Carme Castellano Josefina Pons Jordi García-Antón Xavier Solans Mercè Font-Bardía Josep Ros 《Inorganica chimica acta》2008,361(9-10):2923-2928
Reaction of ZnCl2 with N-alkylaminopyrazole ligands 1-[2-(ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[2-(tert-butylamino)ethyl]-3,5-dimethylpyrazole (deat), bis-[(3,5-dimethylpyrazolyl)methyl]ethylamine (bdmae), and bis-[(3,5-dimethylpyrazolyl)ethyl]ethylamine (ddae) in ethanol yields [ZnCl2(NN′)] (NN′ = deae (1), deat (2)), [ZnCl2(bdmae) (3), and [ZnCl(ddae)]2[ZnCl4] (4). These Zn(II) complexes have been characterised by elemental analyses, conductivity measurements and IR and 1H and 13C{1H} spectroscopy. The NMR studies proved the flipping of the six-membered ring. The solid of complexes 1, 2, and 4 were determined by X-ray diffraction studies. The Zn(II) is coordinated to the deae and deat ligands by one nitrogen atom of the pyrazolyl group and one nitrogen atom of the amine, and to bdmae ligand by two nitrogen atoms of the pyrazolyl groups, along with two chlorine atoms in a tetrahedral geometry. With ddae ligand, the Zn(II) is coordinated by two nitrogens atoms of the pyrazolyl groups and one nitrogen atom of the amine, along with one chlorine atom, in a tetrahedral geometry. 相似文献
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31P NMR chemical shifts of salts of adenosine 5′-triphosphate and diphosphate: ATPH2?22(Me4N+) · H2O, ATPH2?22 Na+ · 3.5 H2O, ATPH2?2Mg2+ · 4 H2O, ATPH2?2Ca2+ · 2 H2O, ADPH2?2(Me4N+) · H2O and ADPH2?Mg2+ · 4 H2O have been measured in 0.02 M 2H2O solutions at 145.7 MHz (22° C) at constant p2H values (8.20 and 6.20). The results are compared with those obtained from salts of adenosine 5′-monophosphate and other simpler phosphomonoesters, e.g. AMP2?2(Me4N+), AMP2?Mg2+, AMPH?Me4N+ and (AMPH?)2Mg2+. It is concluded that the effects exerted by Mg2+ and Ca2+ on the 31P NMR shifts of dipoly- and tripolyphosphates relative to monovalent cations are due mainly to changes in conformation of the polyphosphate chain rather than to purely electronic factors associated with the binding of divalent cations to the phospho-oxyanions. The data are consistent with the existence of the following complexes at p2H 8.20: (MgPαPβ)ADP? and (MgPαPγ)ATP2?af (MgPαPβ)ATP2?af (MgPβPγ)ATP2? with the latter equilibrium relatively fast in the NMR time scale. Monoprotonation of the terminal phosphate appears to weaken the Mg2+-polyphosphate binding, particularly at Pβ of MgADPH and at Pβ and Pγ of MgATPH?. The Mg2+-polyphosphate binding weakens further at p2H 3.70, i.e. in MgATPH2. Possible implications of the results in the mechanism of actomyosin Mg2+-ATPase in muscle contraction are discussed. 相似文献
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Takao Naganuma Shinichi Nakagawa Akie Tanigawa Yasnory F Sasaki Naoki Goshima Tetsuro Hirose 《The EMBO journal》2012,31(20):4020-4034
Paraspeckles are unique subnuclear structures built around a specific long noncoding RNA, NEAT1, which is comprised of two isoforms produced by alternative 3′-end processing (NEAT1_1 and NEAT1_2). To address the precise molecular processes that lead to paraspeckle formation, we identified 35 paraspeckle proteins (PSPs), mainly by colocalization screening with a fluorescent protein-tagged full-length cDNA library. Most of the newly identified PSPs possessed various putative RNA-binding domains. Subsequent RNAi analyses identified seven essential PSPs for paraspeckle formation. One of the essential PSPs, HNRNPK, appeared to affect the production of the essential NEAT1_2 isoform by negatively regulating the 3′-end polyadenylation of the NEAT1_1 isoform. An in vitro 3′-end processing assay revealed that HNRNPK arrested binding of the CPSF6–NUDT21 (CFIm) complex in the vicinity of the alternative polyadenylation site of NEAT1_1. In vitro binding assays showed that HNRNPK competed with CPSF6 for binding to NUDT21, which was the underlying mechanism to arrest CFIm binding by HNRNPK. This HNRNPK function led to the preferential accumulation of NEAT1_2 and initiated paraspeckle construction with multiple PSPs. 相似文献
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《Inorganica chimica acta》1986,123(2):87-90
Derivatives of Co(II), Ni(II), Cu(II) and Zn(II) with 3′AMP and 2′AMP were synthesized and characterized by IR UV-Vis and fluorescence spectroscopy. There seems to be bonding of the metal ion to the base in all cases. The activation test, using the complexes as allosteric labels, was carried out with rabbit muscle glycogen phosphorylase b, but the enzyme was not activated, confirming that the phosphate group must necessarily be bonded to position 5′ of the ribose in order to activate this enzyme. 相似文献
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《Bioscience, biotechnology, and biochemistry》2013,77(8):1225-1229
Interactions between auxin–binding protein–I (ABP–I), purified from etiolated mung bean seedlings, and nuclear components from mung bean tissues were investigated. When NaCI–solubilized components of chromatin were put on an affinity column of ABP–I–Iinked Sepharose 4B, a small amount of the material was retained on the affinity column and was eluted with 1 M NaCl. RNA polymerase II activity was detected in the eluted fraction. Partially purified RNA polymerase II from mung bean nuclei and purified RNA polymerase II from wheat germ also bound to ABP–I. Indole–3–acetic acid was not necessary for the binding of RNA polymerase II to ABP–I. Acid–denatured ABP–I did not bind to RNA polymerase II from wheat germ. The addition of ABP–I to the reaction mixture for RNA synthesis in vitro caused a stimulation of the activity of wheat germ RNA polymerase. 相似文献
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Xiao-Cui Yang Ivan Sabath Jan D?bski Magdalena Kaus-Drobek Micha? Dadlez William F. Marzluff Zbigniew Dominski 《Molecular and cellular biology》2013,33(1):28-37
Animal replication-dependent histone pre-mRNAs are processed at the 3′ end by endonucleolytic cleavage that is not followed by polyadenylation. The cleavage reaction is catalyzed by CPSF73 and depends on the U7 snRNP and its integral component, Lsm11. A critical role is also played by the 220-kDa protein FLASH, which interacts with Lsm11. Here we demonstrate that the N-terminal regions of these two proteins form a platform that tightly interacts with a unique combination of polyadenylation factors: symplekin, CstF64, and all CPSF subunits, including the endonuclease CPSF73. The interaction is inhibited by alterations in each component of the FLASH/Lsm11 complex, including point mutations in FLASH that are detrimental for processing. The same polyadenylation factors are associated with the endogenous U7 snRNP and are recruited in a U7-dependent manner to histone pre-mRNA. Collectively, our studies identify the molecular mechanism that recruits the CPSF73 endonuclease to histone pre-mRNAs, reveal an unexpected complexity of the U7 snRNP, and suggest that in animal cells polyadenylation factors assemble into two alternative complexes—one specifically crafted to generate polyadenylated mRNAs and the other to generate nonpolyadenylated histone mRNAs that end with the stem-loop. 相似文献