Non-canonical targets destabilize 토토 승무패s in human Argonautes

토토 승무패 is short 20-22-nucleotide RNA molecules. Unlike the messenger RNA (mRNA), 토토 승무패 is a type of non-coding RNA that is not translated into protein. These 토토 승무패s bind complementarily to the mRNA sequence through the 2nd to 7th "seed site" from the 5' terminal of the 토토 승무패 sequence and inhibit the synthesis of proteins encoded by the mRNA. Therefore, 토토 승무패s 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 토토 승무패 recognizes and inhibits its target mRNA, and the expression control mechanisms of 토토 승무패s in plants and animals.

Target recognition by 토토 승무패s in animals begins with the loading of 토토 승무패s into Argonaute (AGO)-containing effector complexes called RNA-induced silencing complex (RISC) that recognizes the complementary mRNA sequence. This 토토 승무패-mRNA binding through the "seed site" is called a canonical binding. Sequences other than the 토토 승무패 "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 토토 승무패s or targeting mRNAs.

Professor Shin’s research team examined the mechanism of the 토토 승무패 3’ terminal destabilization phenomenon via non-canonical bindings in animal 토토 승무패s using a variety of in vitro assays using biochemical techniques. When a 토토 승무패 binds to a non-canonical targets, a conformational change may occur in the AGO protein. As a result, the 3’ terminal of the 토토 승무패 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 토토 승무패s 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 토토 승무패 often has a great influence in terms of various vital phenomena” and that “the 토토 승무패’s 3’ terminal destabilization mechanism through non-canonical binding is a type of risk management mechanism to minimize target misrecognition from incorrect 토토 승무패 binding and the resulting vital phenomenon malfunctions”. Therefore, he concluded that the results of this study is an “aspect of the “RISCy” business of 토토 승무패. (Here, RISCy has the same pronunciation as “risky” and refers to the RISC complex that is triggered by a 토토 승무패.)

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 토토 승무패 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