Mechanisms determine gene silencing efficacies by miRNAs/siRNAs: thermodynamic properties and secondary structures.

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Kumiko Ui-Tei from The University of Tokyo.

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Date: Wednesday, May 8, 2019

Time: 11:00-12:00

Venue: C016, Level C, Lab 1

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Speaker:

Dr. Kumiko Ui-Tei

Title:
Mechanisms determine gene silencing efficacies by miRNAs/siRNAs: thermodynamic properties and secondary structures.

Abstract:
RNA silencing is a posttranscriptional gene silencing mechanism induced by small non-coding RNAs, such as microRNA (miRNA) or small interfering RNA (siRNA), with approximately 21-23 nucleotides in length. The siRNA loaded on Argonaute (AGO) protein represses the expression of mRNA with its perfect complementary sequence via a mechanism known as RNA interference (RNAi), and also represses multiple mRNAs with only seed sequence (nucleotides 2-8) complementarities via off-target effects. On the other hand, miRNA represses mRNAs with partial complementary sequences through the mechanism similar to off-target effect of siRNA. Although their silencing efficacies are different each other, the determinants of efficacies are unknown. In mammalian cells, we have found that a limited fraction of siRNAs are functional to induce RNAi, and the functional siRNA had thermodynamic asymmetry between both ends to determine the unwinding direction and efficiency. However, the degree of off-target effect by siRNA was revealed to be strongly depended on the thermodynamic stability in the base-pairing between seed region and target mRNA. We also examined the miRNA-mediated silencing efficacies in detail, and found that miRNAs exhibit gradual silencing efficacies by their secondary structures in addition to the thermodynamic stabilities in the seed regions. Furthermore, we found that the biogenesis of miRNA is regulated by several types of double-stranded RNA binding proteins (dsRBPs), which recognize the differences in the secondary structures of miRNAs. It means that the specific types of dsRBP-bound miRNAs are selected to execute their silencing function. These systematic and quantitative analyses may clarify the complicated gene regulatory mechanisms by miRNAs/siRNAs.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit