In eukaryotes, RNA polymerase II (Pol II) is responsible for the synthesis of all mRNAs and myriads of short and long untranslated RNAs, whose fabrication involves close spatiotemporal coordination between transcription, RNA processing and chromatin modification. Crucial for such a coordination is an unusual C-terminal domain (CTD) of the Pol II largest subunit, made of tandem repetitions (26 in yeast, 52 in chordates) of the heptapeptide with the consensus sequence YSPTSPS. Although largely unstructured and with poor sequence content, the Pol II CTD derives its extraordinary functional versatility from the fact that each amino acid in the heptapeptide can be posttranslationally modified, and that different combinations of CTD covalent marks are specifically recognized by different protein binding partners. These features have led to propose the existence of a Pol II CTD code, but this expression is generally used by authors with some caution, revealed by the frequent use of quote marks for the word ‘code’. Based on the theoretical framework of code biology, it is argued here that the Pol II CTD modification system meets the requirements of a true organic code, where different CTD modification states represent organic signs whose organic meanings are biological reactions contributing to the many facets of RNA biogenesis in coordination with RNA synthesis by Pol II. Importantly, the Pol II CTD code is instantiated by adaptor proteins possessing at least two distinct domains, one of which devoted to specific recognition of CTD modification profiles. Furthermore, code rules can be altered by experimental interchange of CTD recognition domains of different adaptor proteins, a fact arguing in favor of the arbitrariness, and thus bona fide character, of the Pol II CTD code. Since the growing family of CTD adaptors includes RNA binding proteins and histone modification complexes, the Pol II CTD code is by its nature integrated with other organic codes, in particular the splicing code and the histone code. These issues will be discussed taking into account fascinating developments in Pol II CTD research, like the discovery of novel modifications at non-consensus sites, the recently recognized CTD physicochemical properties favoring liquid-liquid phase separation, and the discovery that the Pol II CTD, originated before the divergence of most extant eukaryotic taxa, has expanded and diversified with developmental complexity in animals and plants.

在真核生物中，RNA 聚合酶 II (Pol II) 负责合成所有 mRNA 和无数的短和长非翻译 RNA，其制造涉及转录、RNA 加工和染色质修饰之间的密切时空协调。这种协调的关键是 Pol II 最大亚基的一个不寻常的 C 端域 (CTD)，它由七肽的串联重复（酵母中 26 个，脊索动物中 52 个）与共有序列 YSPTSPS 组成。尽管大部分未结构化且序列含量低，Pol II CTD 的非凡功能多功能性源自以下事实：七肽中的每个氨基酸都可以进行翻译后修饰，并且 CTD 共价标记的不同组合被不同的蛋白质结合伙伴特异性识别。这些特征导致提出存在 Pol II CTD 代码，但作者通常谨慎地使用这种表达方式，通过频繁使用“代码”一词的引号来揭示这一点。基于密码生物学的理论框架，这里认为 Pol II CTD 修饰系统满足真正有机密码的要求，其中不同的 CTD 修饰状态代表有机标志，其有机含义是对 RNA 的许多方面做出贡献的生物反应与 Pol II 的 RNA 合成相协调的生物发生。重要的是，Pol II CTD 代码由具有至少两个不同域的适配器蛋白实例化，其中一个域专门用于特定识别 CTD 修改配置文件。此外，Pol II CTD 代码的真实特性。由于不断增长的 CTD 接头家族包括 RNA 结合蛋白和组蛋白修饰复合物，Pol II CTD 代码本质上与其他有机代码集成，特别是剪接代码和组蛋白代码。这些问题将考虑到 Pol II CTD 研究中引人入胜的发展进行讨论，例如在非共识位点发现新的修饰，最近公认的有利于液-液相分离的 CTD 理化性质，以及发现 Pol II CTD，起源于大多数现存真核生物分类群的分化之前，随着动植物的发育复杂性而扩大和多样化。