microRNA and Small interfering RNA (siRNA)
microRNA: microRNA is a short RNA molecule found in eukaryotic cells. A microRNA molecule has very few nucleotides (an average of 22) compared with other RNAs. microRNAs are well conserved in eukaryotic organisms and are thought to be a vital and evolutionarily ancient component of genetic regulation.
microRNAs are post-transcriptional regulators that bind to complementary sequences on target messenger RNA transcripts (mRNAs), usually resulting in translational repression or target degradation and gene silencing. The human genome may encode over 1000 microRNAs, which may target about 60% of mammalian genes and are abundant in many human cell types.
microRNAs show very different characteristics between plants and metazoans. In plants the microRNA complementarity to its mRNA target is nearly perfect, with no or few mismatched bases. In metazoans, on the other hand, microRNA complementarity typically encompasses the 5' bases 2-7 of the microRNA, the microRNA seed region, and thus one microRNA can target many different sites on the same mRNA or on many different mRNAs. In metazoans, the microRNA target sites are in the three prime untranslated regions (3'UTR) of the mRNA. This is how microRNA may target several mRNAs. In plants, targets can be located in the 3' UTR but are more often in the coding region itself.
microRNA has been found to have multiple roles in negative regulation (transcript degradation and sequestering, translational suppression) and possible involvement in positive regulation (transcriptional and translational activation). By affecting gene regulation, microRNAs are likely to be involved in most biological processes. Different sets of expressed microRNAs are found in different cell types and tissues. Aberrant expression of microRNAs has been implicated in numerous disease states, and microRNA-based therapies are under investigation.
Small interfering RNA (siRNA), also known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 nucleotides in length, that play a variety of roles in biology. The most notable role of siRNA is its involvement in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene. In addition, siRNA also acts in RNAi-related pathways, e.g., as an antiviral mechanism or in shaping the chromatin structure of a genome; the complexity of these pathways is only now being elucidated.
siRNAs were first described as part of post-transcriptional gene silencing (PTGS) in plants in 1999. Subsequently, synthetic siRNAs were shown to be able to induce RNAi in mammalian cells. This discovery led to a surge in interest in harnessing RNAi for biomedical research and drug development. siRNAs have a well-defined structure: a short (usually 21-nt) double-strand RNA (dsRNA) with 2-nt 3' overhangs on either end. siRNAs can also be exogenously (artificially) introduced into cells by various transfection methods to bring about the specific knockdown of a gene of interest. In essence, any gene whose sequence is known can, thus, be targeted based on sequence complementarity with an appropriately tailored siRNA. This has made siRNAs an important tool for gene function and drug target validation studies in the post-genomic era.
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