转录完成后,产生的mRNA也不是最终形态,还要受到修饰和编辑。尤其mRNA编辑会改变核苷序列[3],甚至直接把mRNA报废[4]。
“Snapshot” of a typical data set collected using targeted RNA-seq analysis of RPS12 amplicons in this study. Stacked histogram of editing events at each position in RPS12 in a representative replicate sample of RESC6-IP. The cDNA fragment examined is shown as a reference T-stripped sequence (T-str) spanning the internucleotide positions T-str 17 to 151 (see the canonical fully edited RPS12 ORF and 5′ UTR “B-form”sequence in Supplemental Fig. S1). A canonical editing site (ES) for uridine insertion (Ins) or deletion (Del) is just 5′ to a red or a blue non-T nucleotide, respectively. A noncanonical editing site (nES) is just 5′ to a black non-T nucleotide. The representative histogram shows the percentage of RNA-seq reads at each position: ESs with correct insertion (red) or deletion (blue), and incorrect “partial” editing events (yellow). The remaining reads contain a preedited sequence. Editing events at nESs were scored (black). nESs do not require sequence changes in mature transcripts. However, all nESs at steady state carried editing events in our samples. The start codon (box) includes T-str positions 30–31 and requires editing at T-str 31 (ES72). The stop codon (box) includes T-st 151 (ES3) and requires editing at this position [3].
在翻译时,有些病毒能让核糖体跳过几个核苷,翻译出跟mRNA序列不一样的肽链 [5, 6]。
一个基因编码产生的mRNA也不总是一样的,Alternative splicing是个前沿话题,到底是不是一定产生同一种肽链还很难说,可能并不是。
Common mechanisms of alternative splicing. Alternative splicing can occur although a number of different processes and give rise to different mature transcripts (right). Exons and final transcripts are illustrated as boxes while lines represent introns. Constitutively expressed exons are depicted in green, and alternatively spliced exons are depicted in blue or brown. Retained introns occur with the absence of splicing, with the intervening intron (black) included in the final transcript.[1]
一些非编码RNA引导剪接复合体跳过一段序列,即内含子,调控信号有很多文章论述,但仍不完全清楚[1,2]。
Exon and Intron Definition Interactions (A) Schematic of spliceosomal components and regulatory proteins that participate in exon and intron definition and interactions between them. Trans-acting splicing factors are shown as blue shapes, and their names are shown next to the shape. The RS domain is marked by “RS.” Blue arrows denote intron or exon definition interactions, many of which are mediated by the RS domain. Exons are represented as gray boxes, intronic RNA and snRNAs as gray lines, and cis-acting motifs as colored lines, with the consensus sequences of these motifs shown underneath. The pairing of U1 snRNA with the 5′ splice site is indicated by black lines. (B) Schematic of microexon definition, shown in the same manner as described in (A).
我觉得吧,中学就是学习适合中学的常识性内容,国内特别喜欢考概念辨析,我只想说清谈误国,有个了解就行了,世界上什么东西没有例外?但也没必要卡在一些边边角角钻牛角尖,毕竟最后会攻读RNA方向的PhD也没多少人。
观其大略,把握有用信息,是个重要的技能。"亮在荆州,以建安初与颍川石广元、徐元直、汝南孟公威等俱游学,三人务於精熟,而亮独观其大略。每晨夜从容,常抱膝长啸,而谓三人曰:卿诸人仕进可至郡守刺史也。三人问其所志,亮但笑而不言。" -- 三国志-诸葛亮传,裴松之注
Reference
[1] Chen, J., Weiss, W. Alternative splicing in cancer: implications for biology and therapy.Oncogene34,1–14 (2015). https://doi.org/10.1038/onc.2013.570
[2] Jernej Ule, Benjamin J. Blencowe, Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution, Molecular Cell, Volume 76, Issue 2, 2019, Pages 329-345, ISSN 1097-2765
[3] Vikas Kumar, Alasdair Ivens, Zachary Goodall, Joshua Meehan, Pawan Kumar Doharey, Andrew Hillhouse, Daniel Osorio Hurtado, James J. Cai, Xiuren Zhang, Achim Schnaufer and Jorge Cruz-Reyes. Site-specific and substrate-specific control of accurate mRNA editing by a helicase complex in trypanosomes. RNA. 2020 Dec;26(12):1862-1881. doi: 10.1261/rna.076513.120. Epub 2020 Sep 1.
[4] Lindeboom, R.G.H., Vermeulen, M., Lehner, B.et al.The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy.Nat Genet51,1645–1651 (2019). https://doi.org/10.1038/s41588-019-0517-5
[5] Luke GA, de Felipe P, Lukashev A, Kallioinen SE, Bruno EA, Ryan MD. *Occurrence, function and evolutionary origins of '2A-like' sequences in virus genomes*. J Gen Virol. 2008 Apr;89(Pt 4):1036-42.
[6] Doronina VA, de Felipe P, Wu C, Sharma P, Sachs MS, Ryan MD, Brown JD. Dissection of a co-translational nascent chain separation event. Biochem Soc Trans. 2008 Aug;36(Pt 4):712-6.
二十世纪的大量科学实验显示,原核生物的一些 mRNA 是多顺反子,一个 mRNA 同时编码数种多肽链,不同的多肽链编码序列由较短的、不编码蛋白质的间隔序列分开。许多病毒核酸转录出的 mRNA 也是多顺反子。
因此,“一个 mRNA 只能指导合成一种多肽链”是被实验证伪的假命题。
在此基础上,你可以很容易地想到:
这不仅指“人类的科技能轻易创造真核多顺反子”。莱茵衣藻、Chofmochloris zofingiensis 等根正苗红的真核生物能整出数百个多顺反子,能从一个 mRNA 翻译出 2、3 个蛋白质。
可以看看相关文献:
Widespread polycistronic gene expression in green algae.
Sean D. Gallaher, Rory J. Craig, Iniyan Ganesan, Samuel O. Purvine, Sean R. McCorkle, Jane Grimwood, Daniela Strenkert, Lital Davidi, Melissa S. Roth, Tim L. Jeffers, Mary S. Lipton, Krishna K. Niyogi, Jeremy Schmutz, Steven M. Theg, Crysten E. Blaby-Haas, Sabeeha S. Merchant.
Proceedings of the National Academy of Sciences. Feb 2021, 118 (7) e2017714118;
DOI: 10.1073/pnas.2017714118
如果教科书说“真核生物一个 mRNA 只能指导合成一种多肽链”是对的,那意味着教科书上的信息是过时的。教科书的编者可能还不知道这件事,或是知道了但还没来得及修改。