前体RNA在SF3B1突变敏感的神秘3'拼接部位的结构模式
Austin Herbert1, Abigail Hatfield1, Alexandra Randazza1
1Department of Genetics and Biochemistry, Center for Human Genetics, Clemson University.
bioRxiv : the preprint server for biology
|March 3, 2025
概括
在血液疾病中的SF3B1突变会导致变化的拼接. 对于SF3B1敏感的拼接点具有独特的序列和结构特性,导致错误拼接.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 在RNA分离过程中.
背景情况:
- SF3B1对结合体功能至关重要,其突变在骨髓质疏松综合征中很常见.
- 在SF3B1中经常观察到K700E突变,导致加密3'拼接部位的使用增加.
- 了解SF3B1敏感拼接接口的特性是阐明疾病机制的关键.
研究的目的:
- 确定和描述受SF3B1 K700E突变影响的拼接接口的序列和结构性质.
- 为了区分SF3B1敏感的拼接部位和SF3B1耐药的密码拼接部位.
- 调查RNA结构可访问性在SF3B1介导的拼接改变中的作用.
主要方法:
- 在SF3B1 K700E突变中错误拼接的192个核心拼接接口的识别.
- 基于序列和RNA结构的SF3B1敏感和SF3B1抗性密码拼接位点的比较.
- 对敏感和抗性结点的RNA结构可访问性的实验性确定.
主要成果:
- 对SF3B1敏感的加密3'拼接部位表现出明显的序列特征,包括延长的聚胺基通道和较弱的拼接部位强度.
- 虽然NAG基因的RNA结构可访问性模式在各个结类型中都是相似的,但SF3B1敏感位点在结构上与正规位点的区别较小.
- 与耐SF3B1连接相比,SF3B1敏感的拼接连接显示出更大的整体灵活性.
结论:
- 对SF3B1敏感的拼接接口具有独特的序列和结构特征,具有弱且差异化不良的拼接位.
- 这些特性有助于在存在SF3B1突变的情况下改变3'连接部位的识别.
- 这些发现提供了关于SF3B1突变血液疾病中拼接缺陷的分子基础的见解.
相关概念视频
RNA Splicing
55.9K
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...
55.9K
Alternative RNA Splicing
20.9K
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...
20.9K
Pre-mRNA Processing: RNA Splicing
5.2K
5.2K
Leaky Scanning
5.1K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.1K
pre-mRNA Processing
52.5K
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...
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...
52.5K
Pre-mRNA Processing: Modification of pre-mRNA Ends
9.1K
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...
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...
9.1K


