小柯机器人

美国哥伦比亚大学Stavros Lomvardas研究小组发现，RNA介导的对称性破坏实现单一嗅觉受体的选择。相关论文于2023年12月20日在线发表在《自然》杂志上。

研究人员表示，嗅觉受体（OR）选择是等位基因竞争转录优势的一个极端例子，每个嗅觉神经元都能稳定转录约2000个或更多OR等位基因中的一个。OR基因的选择是由多染色体增强子枢纽介导的，它能激活单个OR基因的转录，然后由依赖于OR基因翻译的反馈来稳定这种选择。

研究人员使用单细胞基因组学方法展示了许多具有不同增强子组成的竞争性中心的形成，其中只有一个中心保留了常染色质特征和转录能力。此外，研究人员还提供了证据，证明增强子转录招募了增强子并在局部加强了增强子中心的活性，而增强子RNA则抑制了竞争性增强子的远距离转录，促进了向转录单一性的过渡。

OR转录足以打破等位增强子中枢之间的对称性，而OR翻译则能稳定占主导地位的中枢的转录，这表明OR等位基因可能存在连续的非编码和编码机制，以实现转录的普遍性。研究人员提出，编码的OR mRNA具有影响核结构、增强自身转录和抑制竞争者转录的非编码功能，这对细胞命运的概率决定具有普遍意义。

附：英文原文

Title: RNA-mediated symmetry breaking enables singular olfactory receptor choice

Author: Pourmorady, Ariel D., Bashkirova, Elizaveta V., Chiariello, Andrea M., Belagzhal, Houda, Kodra, Albana, Duffi, Rachel, Kahiapo, Jerome, Monahan, Kevin, Pulupa, Joan, Schieren, Ira, Osterhoudt, Alexa, Dekker, Job, Nicodemi, Mario, Lomvardas, Stavros

Issue&Volume: 2023-12-20

Abstract: Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, where every olfactory neuron stably transcribes one of approximately 2,000 or more OR alleles1,2. OR gene choice is mediated by a multichromosomal enhancer hub that activates transcription at a single OR3,4, followed by OR-translation-dependent feedback that stabilizes this choice5,6. Here, using single-cell genomics, we show formation of many competing hubs with variable enhancer composition, only one of which retains euchromatic features and transcriptional competence. Furthermore, we provide evidence that OR transcription recruits enhancers and reinforces enhancer hub activity locally, whereas OR RNA inhibits transcription of competing ORs over distance, promoting transition to transcriptional singularity. Whereas OR transcription is sufficient to break the symmetry between equipotent enhancer hubs, OR translation stabilizes transcription at the prevailing hub, indicating that there may be sequential non-coding and coding mechanisms that are implemented by OR alleles for transcriptional prevalence. We propose that coding OR mRNAs possess non-coding functions that influence nuclear architecture, enhance their own transcription and inhibit transcription from their competitors, with generalizable implications for probabilistic cell fate decisions.

DOI: 10.1038/s41586-023-06845-4

Source: https://www.nature.com/articles/s41586-023-06845-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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