长非编码反意义RNA通过嵌入的SINEB2重复控制Uchl1翻译.
Claudia Carrieri1, Laura Cimatti, Marta Biagioli
1Area of Neuroscience, International School for Advanced Studies (SISSA), via Bonomea 265, 34136 Trieste, Italy.
Nature
|October 16, 2012
概括
研究人员发现了一种新型的长非编码RNA (lncRNA),可以调节基因表达. 这种反意义的Uchl1 lncRNA增强了蛋白质合成,揭示了一种新的转录后基因控制层.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 大多数哺乳动物基因组被转录,产生各种RNA分子,包括长非编码RNA (lncRNAs).
- 核丰富的ncRNAs通常具有未知的功能,尽管一些反意义 lncRNAs通过感觉-反意义配对来调节基因表达.
- 乌比奎丁碳氧终端酶L1 (Uchl1) 对大脑功能至关重要,并与神经退行性疾病有关.
研究的目的:
- 为了识别和描述新的核丰富 lncRNAs.
- 调查Uchl1基因新发现的lncRNA反义的功能.
- 为了阐明Uchl1蛋白合成的调节机制.
主要方法:
- 使用转录组分析识别核丰富的lncRNAs.
- 对反意义Uchl1RNA与Uchl1mRNA的相互作用进行实验验证.
- 在各种条件下评估Uchl1蛋白水平,包括mTORC1抑制.
- 分析RNA局部化和多元体关联.
主要成果:
- 一个新的核丰富的lncRNA,反意义Uchl1被确定.
- Antisense Uchl1 在转录后增强了Uchl1蛋白质的合成.
- 其活动依赖于5'重叠序列和嵌入的SINEB2元素.
- 拉巴胺素诱导的mTORC1抑制增加了UCHL1蛋白质,通过促进反意义UCHL1出口到细胞质,从而促进翻译.
结论:
- 一个新的功能性lncRNAs类别,反意义Uchl1,已被确定.
- 反理性Uchl1调节Uchl1蛋白合成在转录后的水平.
- 压力信号通路调节反意义的UCHL1活动,影响UCHL1的翻译,并揭示了一个新的基因表达控制机制.
相关概念视频
02:30siRNA - Small Interfering RNAs
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 ATP-dependent...
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 ATP-dependent...
01:29Translational Regulation
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
02:39lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA (lncRNA)...
02:28Leaky Scanning
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 stands for...