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1) Interestingly, Robo3.1 is an axon-directed receptor that plays an important role in the midline crossing of the spinal commissural axons. During the study of axon explant growth, the authors found that the decrease in Robo3.1 in the joint axons after the crossover was dependent on the floor plate, and this decline occurred mainly at the protein level.
2) In order to study the secret behind this protein regulation, the authors first considered several members of the YTHDF family, because these proteins can always regulate the translation and stability of mRNA by binding to methylation sites. First look at whether Robo3.1 mRNA is likely to undergo methylation modification, MeRIP-seq high-throughput sequencing data, SRAMP (predicted results), MeRIP-pcr three ways to help study to determine the target gene Robo Methylation site on 3.1. The revelation given here is how to prove that the methylation modification on an RNA molecule does exist? Three steps, first MeRIP methylation sequencing to determine the methylation potential region, and then SRAMP tool to predict the methylation site credibility Whether, in the end, MeRIP-PCR verification plus mutation verification, such a process can fully explain the true presence of methylated regions. 
1) This time, methylation modification of CDS can be seen from the figure. In fact, the methylation modification that occurs at the GGAC motif position in the Exon2 region ultimately plays a key role. 
RNA methylation research continues to heat up, high-scoring articles continue to emerge, but research ideas tend to be diversified, and more articles are not limited to exploring the methylation modification resulting in a decrease in RNA stability to explain a biological phenomenon, which is shared today. These two articles explain why a biological process changes due to changes in methylation modification from the perspective of protein translation. Of course, this has to mention Reader YTHD1, which is due to the fact that the Reader protein can promote this. The protein translation efficiency of m6A-modified mRNA was significantly enhanced. In the future public number, Xiao Bian will also bring you more cutting-edge RNA m6A methylation research consultation, and provide new ideas for everyone's research and development. 
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What did the big cows study in 2019? —m6A article inventory
In 19 years, it has been quietly nearly half, but the research on RNA methylation does not stop. In the past one and a half months, there have been more than a dozen high-scoring articles. Nature and Cell have published related articles; hematopoietic stem cell differentiation, cancer cell epithelial-mesenchymal transition, dendritic cell activation, cardiomyocyte hypertrophy, endogenous The immune response regulation has its own figure. Here, Xiaobian will show you some of the latest m6A RNA methylation research results, to see how this research hotspot is presented in several big cattle topics, give you an RNA m6A methylation year. inventory.
Are you still obsessed with writers, erasers? Are you still seeking m6A-mediated degradation of mRNA? We first choose the two most unique studies in the near future and share them with you. The article "The m6A reader YTHDF1 regulates axon guidance through controlal control of Robo3.1 expression", published in the field of nucleic acid research, reveals the relationship between methylation and protein translation from another perspective, "RNA m6A" published by Nature Communication. Methylation regulates the epithelial mesenchymal transition of cancer cells and translation of Snail", which emphasizes the different 3'UTRs in the past, and the methylation modification occurring in the CDS region also has important regulatory significance.
Article 1: Writer or Eraser? No, this time we look at Reader
Do you hate METTL14, METTL3, FTO or ALKBH5? This time we look at how this article does the Reader protein. Reader protein can specifically recognize the methylation site to bind to it and play a biological function, although it is far less concerned with methylation (Writer) or demethylase (Eraser), but in fact Reader It is the direct identifier of the methylation site, and its status is more important. The article published in this Nucleic Acid clearly states that Reader is able to bind to an important gene, Robo3.1, which is methylated and related to Axon Guidance.
3) According to the RIP-pcr of YTHDF1, YTHDF1 can bind to Robo3.1 mRNA by recognizing the methylation site, and after the mutation of the methylation site, the binding signal disappears, indicating that YTHDF1 can recognize Robo3. 1 methylation site. And one of the important functions of YTHDF1 is that it can improve the translation efficiency of mRNA. After transferring Robo3.1 and YTHDF1 and the Robo3.1 plasmid with methylation site mutation, it is found that YTHDF1 promotes protein through the assembly of m6A sites. The effect of translation is very obvious. The Robo3.1 presented in the last article relies on basal protein changes, in fact, because the basal changes YTHDF1 and regulates the protein expression of Robo3.1.
Article 2: 3'UTR? No, this time it is more important for CDS.
Have you ever wondered where the m6A modification is more important in the mRNA? Remember the article by Dr. He Chuan in the study of Foxm1 methylation in glioma stem cells? ALKBH5 is highly expressed in glioma samples, and ALKBH5 regulates the methylation site of pre-Foxm1 in the 3'UTR region to affect the stability of Foxm1 mRNA.
Does methylation necessarily occur in the 3'UTR region of mRNA to play an important role? The story in this Nature Communication article is different. Epithelial-mesenchymal transition is an important step in cancer cell metastasis. During this process, the m6A level of mRNA is increased, and the silence of METTL3 can block the metastasis, invasion and EMT process of cancer cells. . Snail is an important methylation target of METTL3, this time not the UTR region of Snail, but the m6A methylation modification of the CDS region initiates polyribosome-mediated translation of Snail mRNA, interestingly similar to the previous one. In this article, YTHDF1 also binds and regulates the methylation site of this region, which promotes the protein translation efficiency of the gene. In Xiaobian's view, this article is definitely the best one in the current study of m6A modification function.
2) Does the modification occur in the precursor or mature body? You must have had similar questions. Let's look at the half-lives of precursor RNA and matures. The results in this article show that the half-lives of both precursors and matures have decreased, indicating that methylation may occur before. On the body RNA.
3) YTHDF1 YTHDF2 regulates a certain molecule at the same time. Snail is the mRNA molecule that is mainly discussed in this article. This molecule is essentially regulated by two aspects. YTDHF2 binds to the RNA part of the precursor to affect the stability of the molecule. YTHDF1 can bind and enhance the translation of the protein. Efficiency, both aspects have been confirmed on the same molecule.
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