Baralle Marco, Baralle Francisco Ernesto
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Italy.
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Italy.
Biosystems. 2018 Feb;164:39-48. doi: 10.1016/j.biosystems.2017.11.002. Epub 2017 Nov 6.
This issue dedicated to the code of life tackles very challenging and open questions in Biology. The genetic code, brilliantly uncovered over 50 years ago is an example of a univocal biological code. In fact, except for very few and marginal variations, it is the same from bacteria to man, the RNA stretch: 5' GUGUUC 3' reads as the dipeptide: Val-Phe in bacteria, in yeast, in Arabidopsis, in zebra fish, in mouse and in human. A degree of ambiguity is possible if mutations are introduced in the tRNAs in a way that the anticodon reads one amino acid but the aminoacyl-transferase attaches a different one onto the tRNA. These were the very useful suppressor genes that aided greatly the study of bacterial genetics. Other biological codes however, are more akin to social codes and are less amenable to an unambiguous deciphering. Legal and ethical codes, weather we like it or not, are flexible and depend on the structure and history of the society that has produced them, as well as a specific point in time. The codes that govern RNA splicing have similar characteristics. In fact, the splicing code depends on a myriad of different factors that in part are influenced by the background in which they are read such as different cells, tissues or developmental stages. Given the complexity of the splicing process, the construction of an algorithm that can define exons or their fate with certainty has not yet been achieved. However a substantial amount of information towards the deciphering of the splicing code has been gathered and in this manuscript we summarize the point reached.
本期致力于生命密码的特刊探讨了生物学中极具挑战性且尚无定论的问题。50多年前出色地被揭示的遗传密码就是一种明确的生物密码的范例。事实上,除了极少数边缘性变异外,从细菌到人类,遗传密码都是相同的,即RNA片段:5' GUGUUC 3'在细菌、酵母、拟南芥、斑马鱼、小鼠和人类中都编码二肽:Val-Phe。如果以某种方式在tRNA中引入突变,使得反密码子读取一种氨基酸,但氨酰基转移酶却将另一种氨基酸连接到tRNA上,就可能出现一定程度的模糊性。这些就是非常有用的抑制基因,极大地促进了细菌遗传学的研究。然而,其他生物密码更类似于社会密码,不太容易进行明确的解读。法律和道德规范,无论我们是否喜欢,都是灵活的,取决于产生它们的社会结构和历史,以及特定的时间点。调控RNA剪接的密码也有类似的特点。事实上,剪接密码取决于众多不同因素,这些因素部分受到其解读背景的影响,比如不同的细胞、组织或发育阶段。鉴于剪接过程的复杂性,尚未实现构建一种能够确定地定义外显子或其命运的算法。然而,已经收集了大量关于解读剪接密码的信息,在本手稿中我们总结了目前所达到的程度。