Mystery behind mRNA Modifications begins to Unravel

Research led scientists at the University of Birmingham, investigating the purpose of modifications found at the beginning of messenger RNA chains have been able to come up with insights into their purpose which were previously unknown.

Messenger RNAs (mRNAs), vital for protein production, are protected by a cap structure at the beginning of the chain which also influence how messenger RNA produces proteins. It is the first few nucleotides of the cap structure of an mRNA which carry the modifications called methylation. These occur in animals as well as in some of their parasites like SARS viruses and trypanosomes.

来自伯明翰大学、牛津大学、诺丁汉大学和华威大学的研究人员成功地创建了一个“敲除模型”，从果蝇(Drosophila)中删除了两个关键基因，他们能够证明这两种酶在动物的奖励学习过程中发挥了重要作用。这些果蝇在学习特定气味与糖奖励之间的联系的能力上存在缺陷，这突显了当果蝇没有甲基化过程中使用的两种酶时发生的情况。

Lead author Dr Matthias Soller from the School of Biosciences at the University of Birmingham says:

“The study shows us that mRNA modifications have important functions in the brain. Even though these flies are alive, they are not very capable of learning essential survival skills.”

这项研究建立在该论文的共同作者之一、诺丁汉大学的鲁伯特·弗赖教授之前所做的工作的基础上，他发现，在小鼠身上，上限的修改是高度动态的。

The team discovered that these modifications played a role in transporting the mRNAs to synapses – the site of communication between neurons.

牛津大学神经回路与行为研究中心的斯科特·瓦德尔教授说:“这种学习表型引出了许多新问题。虽然我们还不知道潜在神经元功能障碍的详细性质，但这让人想起与脆性X智力障碍蛋白FMRP相关的遗传疾病，它也涉及RNA生物学，已知会在突触发育和可塑性中产生缺陷。”

Dr Irmgard Haussmann from Birmingham City University added: “Analysing the cap modifications is very challenging and further technical hurdles need to be taken to look at modifications in specific mRNAs.”

“This is highly relevant as SARS and other viruses that have their own cap methylation enzyme, but it is not really understood what role this plays in virus-host interactions,” commented Dr Nathan Archer from the University of Nottingham School of Veterinary Medicine and Sciences.

该团队的下一步将更详细地研究修饰的mRNA能够影响与奖励学习和病毒传播相关的蛋白质表达的机制。

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