在前mRNA拼接中,脊髓肌肉缩疾病基因产物SMN的新功能
L Pellizzoni1, N Kataoka, B Charroux
1Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.
Cell
|December 9, 1998
概括
脊髓肌肉缩 (SMA) 与运动神经元 (SMN) 蛋白质的生存有关,这对于mRNA前拼接至关重要. 这项研究揭示了SMN.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
背景情况:
- 脊髓肌肉缩 (SMA) 是一种神经退行性疾病,由运动神经元 (SMN) 蛋白质水平或突变的生存率降低引起.
- 在细胞质中,SMN蛋白对结合体小核核核糖核蛋白 (snRNP) 组合至关重要,并且存在于核宝石中.
研究的目的:
- 研究SMN蛋白在mRNA前拼接中的作用及其与SMA的联系.
- 确定SMN突变如何影响其在拼接机械中的功能.
主要方法:
- 利用一种主导负的SMN突变 (SMNdeltaN27) 来研究其对核snRNP的影响.
- 使用野生型SMN,SMNdeltaN27和SMA患者衍生的SMN突变体进行了体外剪接试验.
主要成果:
- SMNdeltaN27引发了核 snRNP 的重大重组.
- 在实验室中,SMNdeltaN27抑制了mRNA前拼接,而野生型SMN则表现出刺激作用.
- 与SMA相关的SMN突变未能刺激拼接.
结论:
- SMN蛋白对于产生前mRNA拼接机制至关重要.
- 这种SMN的功能对于信使RNA (mRNA) 生物发生是必不可少的.
- 这些发现确定了SMN在拼接中的作用和SMA的发病因子之间的直接联系.
相关概念视频
RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
RNA Splicing
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Alternative RNA Splicing
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
Nonsense-mediated mRNA Decay
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...


