By central dogma in genetic biology, RNAs (ribonucleic acid) are the passive message passengers between DNAs (deoxyribonucleic acid) and proteins. However, with the related findings about non-coding RNA, RNAs are re-recognized about their various roles in creatures now.
Among non-coding RNAs, small silencing RNAs play important roles in gene regulations. There are three different kinds of small silencing RNAs, they are:
- small interfering RNA (siRNA)
- microRNA (miRNA)
- piwi interacting RNA (piwi-RNA)
Small interfering RNAs are double-stranded RNAs with 20-25 base pairs. Mostly, they are exogenous; come from viral infection, transfection, or other means. There are also endogenous origins. For example, convergent transcription, bidirectional transcription, trans-interaction, etc. Those long dsRNAs will be cut into siRNAs by Dicers. SiRNAs are known for their role in RNA interference (RNAi), which interfers with the expression of specific genes with complementary nucleotide sequences. SiRNAs combines with Argonaute proteins to form RISC (RNA-induced silencing complex). RISCs induce mRNA degradation, translational repression or heterochromatin formation.
MicroRNAs are endogenous non-coding RNAs with about 22 base pairs. They are encoded in plants, animals and some DNA virus. MiRNA may be located in “protein-coding” genes (intragenic) or out from genes (intergenic). They are transcribed in the form of pri-miRNA (primary microRNA); then, cut into pre-miRNA by Drosha. Pre-miRNA, which is in hairpin-like structure, are sent to cytosol; cut into miRNA by Dicer. Mature miRNA combines with Ago proteins to form RISC. RISC induce mRNA cleavage or translational repression. You may have noticed that miRNA share similiar roles with siRNA.
Piwi-interacting RNAs are the largest small non-coding RNAs in animal cells. PiRNA are shown in germ line cells, especially testis cells. PiRNAs are generated from long piRNA precursors. They are made with piwi proteins. PiRNAs have important roles in germline developments.
RNAi are related to many gene regulations. They are also potential targets of drug therapies. For instance, miravirsen is anti-miR-122 drug targeted for hepatitis C virus infection. Small silencing RNAs bring hope to disease treatments, but further researches are needed.