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排序方式: 共有719条查询结果,搜索用时 15 毫秒
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Probing the structure and function of U2 snRNP with antisense oligonucleotides made of 2'-OMe RNA 总被引:29,自引:0,他引:29
We have used oligonucleotides made of 2'-OMe RNA to analyze the role of separate domains of U2 snRNA in the splicing process. We show that antisense 2'-OMe RNA oligonucleotides bind efficiently and specifically to U2 snRNP and demonstrate that masking of two separate regions of U2 snRNA can inhibit splicing by affecting different steps in the spliceosome assembly pathway. Masking the 5' terminus of U2 snRNA does not prevent U2 snRNP binding to pre-mRNA but blocks subsequent assembly of a functional spliceosome. By contrast, masking of U2 sequences complementary to the pre-mRNA branch site completely inhibits binding of pre-mRNA. Hybrid formation at the branch site complementary region also triggers a specific change which affects the 5' terminus of U2 snRNA. 相似文献
3.
Antisense oligonucleotides made of 2'-OMe RNA are shown to bind specifically and efficiently to targeted sites on pre-mRNA substrates, allowing affinity selection of splicing complexes using streptavidin/biotin chromatography. The position of probe binding to the pre-mRNA influences which type of splicing complex can be selected. The accessibility of pre-mRNA sequences to antisense probes changes during the course of the splicing reaction. U1, U2, U4, U5 and U6 snRNAs are all detected in affinity-selected mammalian splicing complexes. However, antisense oligonucleotides targeted to snRNAs can block the binding of specific snRNPs to pre-mRNA. Quantitative affinity selection analyses show that only a small fraction of snRNPs in a HeLa nuclear splicing extract participate in spliceosome formation. 相似文献
4.
Mammalian nuclei contain foci which are highly enriched in components of the pre-mRNA splicing machinery. 总被引:65,自引:8,他引:57
M Carmo-Fonseca D Tollervey R Pepperkok S M Barabino A Merdes C Brunner P D Zamore M R Green E Hurt A I Lamond 《The EMBO journal》1991,10(1):195-206
The organization of the major snRNP particles in mammalian cell nuclei has been analysed by in situ labelling using snRNA-specific antisense probes made of 2'-OMe RNA. U3 snRNA is exclusively detected in the nucleolus while all the spliceosomal snRNAs are found in the nucleoplasm outside of nucleoli. Surprisingly, U2, U4, U5 and U6 snRNAs are predominantly observed in discrete nucleoplasmic foci. U1 snRNA is also present in foci but in addition is detected widely distributed throughout the nucleoplasm. An anti-peptide antibody specific for the non-snRNP splicing factor U2AF reveals it to have a similar distribution to U1 snRNA. Co-localization studies using confocal fluorescence microscopy prove that U2AF is present in the snRNA-containing foci. Antibody staining also shows the foci to contain snRNP-specific proteins and m3G-cap structures. The presence of major components of the nuclear splicing apparatus in foci suggests that these structures may play a role in pre-mRNA processing. 相似文献
5.
A I Lamond 《The EMBO journal》1985,4(2):501-507
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Targeted snRNP depletion reveals an additional role for mammalian U1 snRNP in spliceosome assembly 总被引:45,自引:0,他引:45
HeLa cell nuclear splicing extracts have been prepared that are specifically and efficiently depleted of U1, U2, or U4/U6 snRNPs by antisense affinity chromatography using biotinylated 2'-OMe RNA oligonucleotides. Removal of each snRNP particle prevents pre-mRNA splicing but arrests spliceosome formation at different stages of assembly. Mixing extracts depleted for different snRNP particles restores formation of functional splicing complexes. Specific binding of factors to the 3' splice site region is still detected in snRNP-depleted extracts. Depletion of U1 snRNP impairs stable binding of U2 snRNP to the pre-mRNA branch site. This role of U1 snRNP in promoting stable preslicing complex formation is independent of the U1 snRNA-5' splice site interaction. 相似文献
8.
正常小鼠高频心电图时域值和功率谱的研究 总被引:5,自引:1,他引:4
本文用南京新博公司生产的NHE-1000型心电高频信息检测分析仪研究了正常小鼠(昆明种)高频心电图(HF-ECG)的时域值和QRS波群的功率谱。主要结果如下(以正导为例,-X±SD):心率603±88次/min(n=74);P-R间期相对较长。为34.9±4.7ms(n=58),占心动周期的34.9±4.9%,这与人类有很大的不同;QRS波宽9.2±1.2ms,占心动周期的9.2±1.4%(n=74),这一结果与以前的文献报道相差较大。T波宽10.3±3.2ms,占心动周期的10.3±3.2%;Q-T间期19.4±3.2ms,占心动周期的19.5±3.6%;QRS波群峰-峰值(Vp-p)为1.456±0.480mV;T波高0.336±0.115mV;73只动物Ⅱ导联高频切迹总数只有3个,扭挫26个。Ⅱ导联QRS波群的功率谱特点:0—80Hz的相对能量为45.48±15.32%;80—200Hz为43.97±9.95%;200—300Hz为8.89±7.38%;300—1000Hz为1.66±2.74%。 相似文献
9.
Regulation of mammalian spliceosome assembly by a protein phosphorylation mechanism. 总被引:28,自引:6,他引:22 下载免费PDF全文
Splicing of mRNA precursors (pre-mRNA) is preceded by assembly of the pre-mRNA with small nuclear ribonucleoprotein particles (snRNPs) and protein factors to form a splicesome. Here we show that stimulating Ser/Thr-specific protein dephosphorylation selectively inhibits an early step during mammalian spliceosome assembly. Treatment of HeLa nuclear splicing extracts with human protein phosphatase 1 (PP1) expressed in Escherichia coli, or PP1 purified from rabbit skeletal muscle, prevents pre-spliceosome E complex (early complex) formation and stable binding of U2 and U4/U6.U5 snRNPs to the pre-mRNA. PP1 does not inhibit splicing catalysis if added after spliceosome assembly has taken place. Addition of purified SR protein splicing factors restores spliceosome formation and splicing to PP1-inhibited extracts, consistent with SR proteins being targets regulated by phosphorylation. These data extend earlier observations showing that splicing catalysis, but not spliceosome assembly, is blocked by inhibiting protein phosphatases. It therefore appears that pre-mRNA splicing, in common with other biological processes, can be regulated both positively and negatively by reversible protein phosphorylation. 相似文献