types of introns
ER stress, unfolded protein stress response, 应激情况下发生。这是一个未解的问题。
乐于并善于面对科研中的挑战，往往能在PHD阶段取得成功。
Summary for polyadenylation
- Most eukaryotic RNAs are polyadenylated
- Most eukaryotic undergo APA
RNA decay and gene regulation
- General mRNA turnover pathways
- Aberrant turnover pathways
- Specialized turnover pathways
- Specialized sites of cytoplasmic mRNA turnover
mRNA half-lives in various organisms
- Bacterial, <10 min
- Yeast, 10-20 min
- Mammals: several hours
- rRNA, tRNA 70-120h
tRNA fragment 与表观遗传介导的跨代遗传有关。
计算mRNA半衰期。现在用BRIC-seq、5EU-seq比较多。使用BrU或者5-EU标记mRNA，观察标记的情况。
- 5’-3’ pathway: decapping, XRN1
- 3’-5’ pathway: deadenylation (first phase去除一定长度的polyA，second phase加快去除剩下的polyA)、Exosome外切去除
deadenylation machinery: PAN, CCR4, PARN complex
exosome components
histone RNA 没有polyA
Aberrant turnover pathways
- 没有stop codon
- 提前产生stop codon
- ribosome卡在mRNA上 no-go mRNA decay：通常通过ribosomal A site招募
- 没有在stop codon停下，还有3’-UTR
Nonsense-Mediated mRNA decay （NMD）
- protect cells from 错误的mRNA
- all eukaryotes
- 30%疾病突变都是由于提前终止
Splicing-dependent and -Independent NMD
- Splicing-dependent 更为常见，90%的stop codon几乎都出现在最后一个exon上，这样可以通过结合在exon上的Exon-junction complex来识别这个mRNA有没有被提前终止。NMD互作的EJ-complex典型的包括UPF1, 2, 3
premature stop mutations in mRNAs
- 基因编辑
- 基因therapy：只能装载<4.5kb的基因片段。
ARE-mediated mRNA turnover
RNA modification
The structure of tRNA and tRNA derived small RNAs
rRNA modification
RNA epigenetics? m6A in mRNA
genome-wide detection methods used to identify RNA modifications
enzymes, MS to identify RNA modifications
m6A pathway and its cellular functions
m6A alters RNA structure to enhance HNRPAC bindings
functional study of the m6A in mouse ESCs
RNA editing, C to U conversion, A to I conversion
RNA editing can change the biochemical and biophysical properties of resulting proteins
章鱼的进化不太依赖于基因组突变，依赖于transcriptome plasticity
UAG⇒UGG，跳过stop codon，治疗癌基因突变。