化RNA的酶性加工
Erich G Chapman1, Victoria J DeRose
1Department of Chemistry, University of Oregon, Eugene, Oregon 97403, USA.
Journal of the American Chemical Society
|January 27, 2010
概括
抗瘤药物西斯丁形成-RNA附加物,破坏RNA处理酶,如基化酶和逆转录酶. 氨酸可以逆转这些-RNA附加物,为未来的研究提供了一个工具.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 西斯是一种广泛使用的抗瘤药物,主要针对DNA.
- 西斯普拉丁与RNA的相互作用及其对RNA加工酶的影响尚不清楚.
- 了解RNA-Pt adducts对于理解基化疗更广泛的细胞效应至关重要.
研究的目的:
- 为了研究二 (Pt(II)) 添加在RNA上如何影响关键RNA加工酶的活性.
- 为了确定[Pt(NH(3)) ((2))) ((2+) -RNA添加剂对基化酶,内啡核核酶和逆转录酶的影响.
- 探索RNA白金化对西斯白金细胞效应的潜在贡献.
主要方法:
- 合成RNA寡核酸与特定的添加物.
- 测试测量3'-->5'和5'-->3'化酶的活性.
- 使用纯素特异性内核酶 (RNase U2) 和逆转录酶的酶分析.
- 使用硫尿素的-RNA添加物的化学逆转.
主要成果:
- 单个Pt(II) 添加在RNA寡核酸上阻断了外核分解性消化.
- 大多数内核核分裂被添加物破坏,RNase U2对GA部位的化有耐受性.
- 在更复杂的RNA结构上 adducts抑制了反转录,表明干扰RNA序列信息传输.
- 尿素被证明可以有效地逆转西斯普拉丁-RNA添加物.
结论:
- 西斯-RNA添加剂显著损害了必不可少的RNA加工酶的功能.
- 引起的RNA处理中断可能会导致西斯的总体细胞毒性.
- 这些发现突出了RNA作为西斯普拉丁的潜在点,并建议RNA处理变化作为作用机制.
- 氨酸为进一步调查青-RNA相互作用提供了有价值的化学工具.
相关概念视频
02:41Chromatin Structure Regulates pre-mRNA Processing
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
01:35Pre-mRNA Processing: Modification of pre-mRNA Ends
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps the cell...
02:01pre-mRNA Processing
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl guanosine). This 5’ cap helps the...
00:58Eukaryotic RNA Polymerases
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
All three eukaryotic RNAPs require specific transcription factors, of which the...
02:53Ribosomal RNA Synthesis
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
02:51mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability