2026年9月2日，美国伊利诺伊大学Alexander S. Mankin等科学家在《自然》（Nature）发表研究，通过工程化嵌合信使-核糖体RNA（mrRNA）和束缚亚基核糖体（Ribo-TM），证明了细菌核糖体能够翻译其自身rRNA编码的蛋白质，为理解翻译起源和正交蛋白生产提供了新平台。

细胞蛋白质合成依赖于核糖体与mRNA之间的随机相遇，这限制了为单一蛋白质生产而优化翻译机制的能力——而这是生物技术中的一个关键需求。一个潜在的解决方案是将蛋白质编码序列整合到核糖体本身中，从而使核糖体专门合成一条多肽。这种整合的可行性也可以解决RNA世界模型中一个长期存在的挑战：解释早期蛋白质合成如何在其组分稀缺且组织不良的情况下仍能可靠运作。核糖体是否能翻译其自身的核糖体RNA（rRNA）仍不清楚。在此，研究人员证明细菌核糖体可以合成其自身RNA中编码的蛋白质。他们通过在16S rRNA上附加一个蛋白质编码序列，工程化了一种嵌合信使-核糖体RNA（mrRNA）。该杂交mrRNA组装成一个小核糖体亚基，与大亚基结合形成Ribo-M——一种能够翻译mrRNA编码蛋白质的核糖体。通过突变或抑制小亚基功能的抗生素可消除翻译，表明mrRNA的翻译是由组装在嵌合mrRNA上的核糖体以顺式方式完成的。将mrRNA整合到具有束缚亚基的核糖体中产生了Ribo-TM，在其中编码、解码和肽合成被统一在一个单一的RNA支架内。这些发现确立了核糖体在体内和体外翻译其自身rRNA的机制可行性，为正交蛋白质生产提供了一个多功能平台，并为翻译的起源提供了见解。

附：英文原文

Title: Rewiring the ribosome to translate proteins encoded in its own RNA

Author: Alizadeh, Kasra, Klepacki, Dorota, Vzquez-Laslop, Nora, Mankin, Alexander S.

Issue&Volume: 2026-09-02

Abstract: Cellular protein synthesis relies on random encounters between ribosomes and mRNAs, limiting optimization of the translation machinery for production of a single protein—a key need in biotechnology. One potential solution is integrating the protein-coding sequence into the ribosome itself, thereby committing the ribosome to synthesis of a single polypeptide. The feasibility of such integration could also address a long-standing challenge in RNA world models: explaining how early protein synthesis could function reliably despite the scarcity and poor organization of its components1. Whether a ribosome can translate its own ribosomal RNA (rRNA) has remained unclear. Here we show that bacterial ribosomes can synthesize proteins encoded within their own RNA. We engineered a chimeric messenger–ribosomal RNA (mrRNA) by appending a protein-coding sequence to 16S rRNA. The hybrid mrRNA assembles into a small ribosomal subunit that binds to the large subunit to form Ribo-M, a ribosome capable of translating mrRNA-encoded proteins. Translation is abolished by mutations or antibiotics that impair the function of the small subunit, demonstrating that mrRNA translation is carried out in cis by ribosomes assembled on the chimeric mrRNA. Incorporating mrRNA into a ribosome with tethered subunits yielded Ribo-TM, in which encoding, decoding and peptide synthesis are united within a single RNA scaffold. These findings establish the mechanistic feasibility of a ribosome translating its own rRNA in vivo and in vitro, offering a versatile platform for orthogonal protein production and insights into the origin of translation.

DOI: 10.1038/s41586-026-10962-1

Source: https://www.nature.com/articles/s41586-026-10962-1