在人类瘤性RNA基因VPS9D1-AS1 (MYU) 中出现并联重复介导的翻译de novo开放阅读框架的出现和延长
Lin Chou1,2,3, Shu-Ting Cho1,2,4,5, Jiwon Lee1,2,5
1Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Genome biology and evolution
|January 13, 2026
概括
新的蛋白质编码基因可以通过翻译从非编码DNA中出现. 这项研究揭示了一个特定的基因orf143是如何通过停止编码子破坏和并联重复扩张延长的,这可能提供瘤抑制的好处.
科学领域:
- 进化生物学 进化生物学
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
背景情况:
- 新的蛋白质编码基因可以从非编码DNA de novo 来产生.
- 基因延长是新基因诞生中的关键步骤,但其机制尚未研究.
- 没有注释的开放阅读框架 (ORF) 可以被翻译和选择,从而产生新的基因.
研究的目的:
- 为了重建新基因c16riboseqorf143 (orf143) 的进化史.
- 调查ORF延长的新机制.
- 在致癌性lncRNA VPS9D1-AS1 (MYU) 的背景下探索orf143翻译的潜在瘤抑制作用.
主要方法:
- orf143.3 的进化重建.
- 分析VPS9D1-AS1结构,包括结合点和并联重复 (TR) 阵列.
- 在癌症患者数据中对orf143区域的体质突变的研究.
主要成果:
- orf143在猿人中通过起始编解子突变产生了de novo,并通过停止编解子破坏突变延长.
- 延长结合了一个TR阵列,在人类群体中经常扩展.
- 转化ORF143可能是瘤抑制的,由ORF区域的体质突变及其与癌症的关联证明.
- 停止密码子破坏和TR阵列扩张被确定为ORF143延长的关键机制.
结论:
- 由停止子破坏和TR扩张等机制驱动的de novoORF延长可以提供选择性优势.
- 在VPS9D1-AS1中,延长的orf143与瘤原体重叠,可能起到瘤抑制作用.
- 这项研究强调了新基因出生的进化途径及其对癌症的潜在影响.
相关概念视频
Leaky Scanning
5.6K
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...
5.6K
Initiation of Translation
38.3K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
38.3K
Initiation of Translation
7.9K
7.9K
Rous Sarcoma Virus (RSV) and Cancer
6.2K
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
6.2K
RACE - Rapid Amplification of cDNA Ends
7.1K
Rapid Amplification of cDNA Ends, or RACE, is one of the most effective methods to obtain a full-length cDNA from an mRNA sequence between a known internal region to the unknown sequence at the 5’ or 3’ end. The unknown region is cloned in the cDNA by a gene-specific primer that binds the known end, and a hybrid primer that attaches a predefined anchor sequence to the unknown end of the cDNA. The sequence in between is amplified by PCR with an anchor primer and a gene-specific...
7.1K
Translation
17.5K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
Translation Produces the Building Blocks of Life
Proteins are...
17.5K


