A whole new picture of RNA epigenetics
The RNA epigenetics "shoulder the handle" teacher he chuan called for a review - this is the first time he has reviewed the hot field in the Cell.
As a primary school student in the circle, I would like to introduce this review article today and write some thoughts on it.
As I mentioned earlier, people are becoming aware of the central role of RNA in central principles.
RNA on more than 100 kinds of modifiers, making it outside the gene sequence information, another layer of control information, therefore, the same transcription, eventually produce the amount of protein and time distribution is very different, the same gene sequence, can also be translated into different sequences of proteins.
Through RNA modification, gene expression in sequence without change appeared difference, people get used to in the backdrop of the epigenetics of RNA modification, this is also my understanding of epigenetics He Chuan teacher of RNA.
Because the protein is the main executor of life activity, direct translation from the mRNA and protein, so for some time, RNA modification research progress is mainly focused on the mRNA, but that doesn't mean RNA modified regulation role is limited to mRNA.
In addition to summarizing the research progress of mRNA modification, this review also analyzed the study of non-coding RNA modification, which is of great benefit to the inspiration researchers.
Various modifications on mRNA
The most familiar one is m6A.
m6A is the most abundant modification in mRNA.
But the amount of mRNA in individual genes has long been limited.
In 2011, Dr Gui-fang jia He Chuan teacher laboratory and Dr FuYe found the first mRNA m6A modify to methyl enzyme - FTO, just announced before the end of the "age" of universe, also open the golden age of RNA modification research.
Other RNA modifiers may be unfamiliar, but they are known as "famous men".
The m1A is extremely abundant on tRNA, and pseudo uracil is the first RNA modified to be found, but until recently it was confirmed that they were also found on mRNA.
The brother of m5C is famous in DNA, and the research in mRNA is more recent.
The most "enigmatic" is mRNA's approach to the ribose 2 'bits of RNA (Am, Um, Cm, Gm) near the 5' end.
In my own experiments, the authors also found that there are many of these modifiers, but their functions are not yet known.
There are recent reports that m6Am modifies the position of 5 'cap, and that the N6 methyl group can also be removed by FTO and affects the stability of mRNA.
MRNA modified methyltransferase, demethylase, and binding protein
m6A modified methyltransferase complex, demethylase (A) and binding protein (B)
Like everything in the universe, the study of RNA modification also takes into account three "philosophical questions" : how it came to be, how it didn't, what it did after it came...
So this is actually how the methyltransferase, the RNA modified, the methylase, the RNA modification, is introduced.
It is useless to say more, the author put these "functional elements" in a form, convenient for the friends to look up.
Especially when it comes to binding proteins or m6A, RNA modification works in three ways.
First, when m6A is in the stem ring structure, it affects the stability of RNA helix, which affects the structure of RNA, which affects the binding of some proteins to RNA, such as HNRNPC and so on.
, on the other hand, some RNA binding protein identification m6A modifications of sites, can be specific to contain m6A RNA, such as a series of YTH family proteins, many researchers, including teacher He Chuan laboratory around this kind of protein function is studied, YTH family protein affected the mRNA precursor processing, protein translation initiation and mRNA degradation and so on many biological processes.
In addition, because of the hydrophobicity of methyl groups, m6A also combines the RNA binding characteristics of some proteins by combining hydrophobic residues.
Especially when it comes to binding proteins or m6A, RNA modification works in three ways.
First, when m6A is in the stem ring structure, it affects the stability of RNA helix, which affects the structure of RNA, which affects the binding of some proteins to RNA, such as HNRNPC and so on.
, on the other hand, some RNA binding protein identification m6A modifications of sites, can be specific to contain m6A RNA, such as a series of YTH family proteins, many researchers, including teacher He Chuan laboratory around this kind of protein function is studied, YTH family protein affected the mRNA precursor processing, protein translation initiation and mRNA degradation and so on many biological processes.
In addition, because of the hydrophobicity of methyl groups, m6A also combines the RNA binding characteristics of some proteins by combining hydrophobic residues.
M6A modifies the regulation of differentiation and development process
RNA modifiers function at the molecular level, and they also affect life processes such as development and disease.
Such as stem cells, directional pedigree and pluripotency genes of mRNA life cycle, are under the control of the m6A modification, when loss of m6A methyl transferase, dry maintenance and differentiation is the process of the disorder.
In zebrafish experiments have shown that the starting stage in embryonic development, from the egg of mRNA depends on m6A binding protein Ythdf2 quickly removed, and replaced by new zygote transcript, phenotype and Ythdf absence can cause developmental delay.
The excessive expression of m6A to methylase, FTO and ALKBH5 can also affect the development of multiple cancers.
Modification of other types of RNA
So far, the study of RNA modification has focused on mRNA.
However, non-coding rnas, including lncRNA, tRNA, rRNA, and so on, are rich in RNA modification, and their functions are poorly understood.
Investigate its reason, on the one hand, because people awareness of non-coding RNA itself also limited (such as lncRNA), on the other hand, people have long put tRNA, rRNA decorated as a dynamic and non reversible constant presence, attention degree is not enough.
Many modifications on tRNA and rRNA
In fact, tRNA is the most richly decorated RNA.
A lot of modification is also very complicated, which needs to be completed through the coordination of various modification enzymes (such as the modification of guanine G and yW etc.).
TRNA 34 (wobble position) and 37 of the most representative, they are on the ring of the tRNA anticodon, for codon - anticodon stability is critical, affect the efficiency and accuracy of protein translation.
In addition to the anti-codon ring, tRNA modification is usually closely related to the structure and affects the stability of tRNA.
Once decorated tRNA is considered to be constant, until recently, has been found tRNA on some sites only partial modification, under pressure, some sites modification level will also change.
Especially He Chuan teacher lab last year, according to a job on the tRNA 58 battle modification is reversible and AlkB family ALKBH1 protein can remove m1A58 methylation modification, this process also affected the stability of the tRNA and protein translation.
RRNA and snRNA also have a lot of RNA modifiers, but they are usually buried deep inside the fold, so the review concludes that these modifications should not be as reversible as the m6A on the mRNA or the m1A58 on tRNA.
However, in the context of environmental factors, immature rRNA and snRNA sites may also have variable modifications.
Conclusion
RNA modification is the key to post-transcriptional regulation. In addition to the sequence and structure of RNA, RNA modification provides another way of tuning gene expression through various binding proteins.
At the molecular level, m6A ACTS as a "accelerator" for mRNA's metabolism, which allows mRNA to be processed faster, translated faster, and eventually degraded faster.
M6A modify mRNA translation have been improved, but the translation product is restricted within the narrower time window, the differentiation and development process for biological is a perfect model, the regulation of genes specifically expressed in a certain stage, its mRNA life be m6A strict control, and complete the efficient protein translation, when growth into the next stage, these mRNA degradation can be quickly again, avoiding interference to the subsequent development.
In addition, for RNA modification of "functional components", such as m6A methyl transferase, enzyme and binding protein, they are how to realize the substrate selectivity, whether you need the assistance of other cofactors, is worth further study.
On the other hand, modification of noncoding RNA is essential for its synthesis, function, and stability.
Many of the tRNA modifications are variable under pressure, and how they affect gene expression in specific situations is also an important aspect of future research.
As mRNA m6A to methyl enzyme FTO found on the arrival of RNA to modify "golden age", that the non-coding RNA, ALKBH1 m1A58 on tRNA to the role of methyl found that also provides a new paradigm for subsequent research.