通过诱导高分子量RNP复合体,多价格的富含GU的寡核酸将TDP-43扣留在核中
Xi Zhang1, Tanuza Das1, Tiffany F Chao2
1Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
iScience
|July 11, 2024
概括
合成的富含GU的RNA可以帮助在核中封存TDP-43 (TAR DNA结合蛋白43),从而有可能治疗TDP-43蛋白病变. 然而,纯的GU重复RNA基因可能会破坏正常的TDP-43功能.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 在RNA生物学,RNA生物学.
背景情况:
- TDP-43 (TAR DNA结合蛋白 43) 的错位化和聚合是神经退行性 TDP-43 蛋白质病变的关键特征.
- 内源核GU丰富的RNAs通常通过抑制其出口而在核中保留TDP-43.
研究的目的:
- 调查合成RNA寡核酸是否可以增强TDP-43的核定位.
- 评估使用外源GU丰富RNA来管理TDP-43错位化的可行性.
主要方法:
- 生物化学分析以比较TDP-43与富含GU的寡核酸结合的情况.
- 细胞通过合成RNA寡核化物 ((GU) 16和Clip34nt) 感染细胞.
- 在转录封锁和RanGAP1消去条件下对TDP-43局部化的评估.
- RNA拉下测试用于识别核糖蛋白 (RNP) 复合体.
主要成果:
- 转染的富含GU的寡核酸,如 (GU) 16,减少了TDP-43的错位化.
- 合成RNA加速了TDP-43核再进口,在诱导细胞质错位后.
- 多价格的GU-oligonucleotides与TDP-43.3形成了高分子量RNP复合体.
- 纯的GU重复寡合物破坏了TDP-43对密码外子的调节,与Clip34nt不同.
结论:
- 外源的多价格GU-RNAs可以有效地促进TDP-43的核定位.
- 虽然对核保留有好处,但纯的GU重复RNA基因可以干扰TDP-43的正常功能.
相关概念视频
piRNA - Piwi-interacting RNAs
6.8K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
6.8K
siRNA - Small Interfering RNAs
16.7K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
16.7K
RNA Interference
26.0K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.0K
Transfer RNA Synthesis
11.9K
One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
11.9K


