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Non-canonical targets destabilize microRNAs in human Argonautes
MicroRNA is short 20-22-nucleotide RNA molecules. Unlike the messenger RNA (mRNA), microRNA is a type of non-coding RNA that is not translated into protein. These microRNAs bind complementarily to the mRNA sequence through the 2nd to 7th "seed site" from the 5' terminal of the microRNA sequence and inhibit the synthesis of proteins encoded by the mRNA. Therefore, microRNAs serve as negative regulators of gene expression.
The biochemistry laboratory led by Professor Shin, Chanseok of the College of Agriculture and Life Science at Seoul National University is investigating the mechanisms by which the microRNA recognizes and inhibits its target mRNA, and the expression control mechanisms of microRNAs in plants and animals.
Target recognition by microRNAs in animals begins with the loading of microRNAs into Argonaute (AGO)-containing effector complexes called RNA-induced silencing complex (RISC) that recognizes the complementary mRNA sequence. This microRNA-mRNA binding through the "seed site" is called a canonical binding. Sequences other than the microRNA "seed site" also bind with mRNA sequences. Such binding where the “seed site” is incomplete are called “non-canonical binding.” Although these non-canonical targets are frequently found in cells, there is not yet enough research on how these non-canonical targets function in terms of regulating the expression of microRNAs or targeting mRNAs.
Professor Shin’s research team examined the mechanism of the microRNA 3’ terminal destabilization phenomenon via non-canonical bindings in animal microRNAs using a variety of in vitro assays using biochemical techniques. When a microRNA binds to a non-canonical targets, a conformational change may occur in the AGO protein. As a result, the 3’ terminal of the microRNA is released from the AGO protein and thus susceptible to degradation by 3’-5’ exonuclease. ..
These results were published in the famous international journal Nucleic Acids Research (NAR) in February of this year under the title “Non-canonical Targets Destabilize microRNAs in Human Argonautes.” It was listed for the first time as a 2017 breakthrough article (a report selected by NAR regarding an eye-opening phenomenon in the field or a paper on answering important questions in the relevant field.).
Professor Shin praised the results of the study by saying “whether or not mRNA expression is inhibited through the microRNA often has a great influence in terms of various vital phenomena” and that “the microRNA’s 3’ terminal destabilization mechanism through non-canonical binding is a type of risk management mechanism to minimize target misrecognition from incorrect microRNA binding and the resulting vital phenomenon malfunctions”. Therefore, he concluded that the results of this study is an “aspect of the “RISCy” business of microRNA. (Here, RISCy has the same pronunciation as “risky” and refers to the RISC complex that is triggered by a microRNA.)
Regarding the direction of future research, Professor Shin ended the interview by stating, “There must be more in-depth research on the detailed biological significance of the microRNA expression control phenomenon through these mechanisms under the actual physiological contexts, such as development, differentiation, and disease.”
Student Reporter Song, Iee-re / Seong, Gayeong
Shin's Research Team>