基本問題：
- RNA的起源、定位和意義
- 明確RNA的各種概念分類
- 各種RNA的基本結構和功能
意義
有一種學說：RNA是生命的起源。
先有雞（DNA）還是先有蛋（蛋白質），好像都不太可能，那有沒有可能先有RNA？橋接了DNA和蛋白質，RNA本身也是一種酶。
分類
首先按是否coding，分coding RNA和non-coding RNA
- Coding RNAs generally refers to mRNA that encodes protein ① to act as various components including enzymes, cell structures, and signal transductors.
- Noncoding RNAs act as cellular regulators without encoding proteins ③.
However, it appears that the boundaries blur between coding RNA and noncoding RNA as
- some coding mRNAs can function without translating to protein via the formation of RNA secondary structure primarily derived from the UTR ② ;
- some lncRNAs can bind with ribosomes, and encode peptides to modulate cellular activities ④.
高中即知的三大類：
- mRNA
- tRNA
- rRNA
non-coding RNA的分類：
- small RNA
- lncRNA
small RNA的分類非常龐大：
- microRNA (miRNA)
- Piwi-interacting RNA (piRNA)
- small interfering RNA (siRNA)
- small nuclear RNA (snRNA) U-RNA
- small nucleolar RNA (snoRNA)
- small rDNA-derived RNA (srRNA)
- tRNA-derived small RNA (tsRNA)
其他RNA：
- Competing endogenous RNAs - ceRNA
- Circular RNA - circRNA
- guide RNA - gRNA
mRNA
真核生物的可變剪切，形成不同的isoform，所以isoform才是蛋白編碼基因的最小單位，一個典型的二維展開。
In eukaryotes, a freshly transcribed RNA transcript is considered a pre-mRNA and needs to undergo maturation to form mRNA. A pre-mRNA contains non-coding and coding regions known as introns and exons, respectively. During pre-mRNA processing, the introns are spliced, and the exons are joined together. A 5’ cap known as 7-methylguanosine is added to the 5’ end of the RNA transcript and the 3’ end is polyadenylated. Polyadenylation refers to the process where a poly(A) tail, which is a sequence of adenine nucleotides, is added to the transcript. The 5’ cap protects the mRNA from degradation, and the 3’ poly(A) tail contributes to the stability of mRNA and aids it in transport.
tRNA
轉運RNA，把特定的氨基酸帶到指定的mRNA密碼子位置。【橋梁中的橋梁：連接mRNA和protein】
Once an amino acid is bound to tRNA, the tRNA is considered an aminoacyl-tRNA. The type of amino acid on a tRNA is dependent on the mRNA codon, which is a sequence of three nucleotides that codes for an amino acid.
rRNA
核糖體的關鍵成分
In eukaryotes, the 40S and 60S subunit form an 80S ribosome. The ribosomes contain an exit (E), peptidyl (P), and acceptor (A) site to bind aminoacyl-tRNAs and link amino acids together to create polypeptides.
Small Nuclear RNA
Small nuclear RNAs (snRNA) are non-coding RNAs that are responsible for splicing introns. The snRNAs join with proteins to form small nuclear ribonucleoproteins (snRNP), which most commonly contain U1, U2, U4, U5, and U6 snRNA molecules. Spliceosome assembly and activity begins once U1 of the snRNP binds a complementary sequence on the 5’ splice site of a pre-mRNA transcript. Introns are then removed from the pre-mRNA transcript by the spliceosome complex and mature mRNA forms.
MicroRNA
MicroRNAs (miRNA) are non-coding RNAs mainly involved in gene regulation. They are mostly processed from introns and are transcribed into primary miRNA from the host gene by RNA polymerase II. They are then modified by endonucleases, such as Drosha and Dicer into a mature miRNA. Studies have shown that miRNAs that bind to an untranslated region (3’UTR) on mRNAs suppress translation, while miRNA binding to promoter regions can upregulate transcription. miRNAs can also function similarly to hormones. They are released into the extracellular fluid and taken up by target cells for regulation of cellular activity. Additionally, researchers are studying these extracellular miRNAs as ideal biomarkers for various diseases. Research has already shown circulating miRNAs to be involved in cancer through its role in controlling oncogenes and tumor suppressors.
Small Interfering RNA
Small Interfering RNAs (siRNA) are double-stranded, non-coding RNAs that inhibit gene expression through RNA interference. They interfere with gene expression by degrading mRNA and preventing the translation of proteins. siRNAs form from long double-stranded RNAs with the assistance of Dicer. Once fully formed, siRNA binds to an RNA induced silencing complex (RISC) and cleaves mRNA through a catalytic RISC protein, Argonaute. Small interfering RNAs have the potential to be therapeutic agents for diseases due to their potency and ability to knock down genes. Unlike miRNAs, siRNAs can specifically target a gene of choice, and a single siRNA guide strand can function multiple times.
參考：
- Coding or Noncoding, the Converging Concepts of RNAs
- Biochemistry, RNA Structure
- Landmark Cell Reviews: Noncoding RNAs
- GPB | 深圳市人民醫院/中科院計算所團隊發表腫瘤免疫單細胞長非編碼RNA圖譜研究
- Single-cell Long Non-coding RNA Landscape of T Cells in Human Cancer Immunity - 參考如何鑒定lncRNA