Modulation of miRISC-Mediated Gene Silencing in Eukaryotes

Abstract

Gene expression is regulated at multiple levels in eukaryotic cells. Regulation at the post-transcriptional level is modulated by various trans-acting factors that bind to specific sequences in the messenger RNA (mRNA). The binding of different trans factors influences various aspects of the mRNA such as degradation rate, translation efficiency, splicing, localization, etc. MicroRNAs (miRNAs) are short endogenous ncRNAs that combine with the Argonaute to form the microRNA-induced silencing complex (miRISC), which uses base-pair complementation to silence the target transcript. RNA-binding proteins (RBPs) contribute to post-transcriptional control by influencing the mRNA stability and translation upon binding to cis-elements within the mRNA transcript. RBPs have been shown to impact gene expression through influencing the miRISC biogenesis, composition, or miRISC-mRNA target interaction. While there is clear evidence that those interactions between RBPs, miRNAs, miRISC and target mRNAs influence the efficiency of miRISC-mediated gene silencing, the exact mechanism for most of them remains unclear. This review summarizes our current knowledge on gene expression regulation through interactions of miRNAs and RBPs.

Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer

“…Furthermore, binding of the translational repressor and decapping activator protein, DDX6, to the miRISC–CCR4–NOT complex has been demonstrated to be a crucial event to reduce stability and translation of the target mRNA [ 26 ]. The core miRISC has also been reported to interact with translation regulators such as GIGYF2, EIF4A1/2 and 4EHP, leading to the repression of target mRNA translation [ 27 ]. Both AGO and GW182 proteins also serve as molecular hubs for multiple ribonucleoprotein complexes (RNPs) or other enzymes involved in RNA metabolism [ 28 , 29 ].…”

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches

“…More particularly, the so-called leading strand (the mature miRNA strand) is merged with the RISC complex, whereas the other is called the passenger strand and is further degraded [ 17 , 18 ]. The miRNA-RISC (miRISC) targets a partially complementary mRNA strand, binding on its 3′untranslated region (3′UTR), while the miRNA sequence that is complementary is called the seed sequence [ 14 , 19 , 20 ].…”

THE SOURCES OF GENOME VARIABILITY AS DOMESTICATION DRIVERS (review)

“…На посттранскрипционном уровне регуляция модулируется различными транс-действующими факторами, которые связываются со специфическими последовательностями в мРНК. Это влияет на различные процессы, такие как скорость деградации и эффективность трансляции мРНК, сплайсинг, локализация (52). МикроРНК в сочетании с ферментом Argonaute образуют комплекс сайленсинга, индуцируемый микроРНК (miRISC, RNA-induced silencing complex), который использует комплементарную нуклеотидную последовательность для подавления транскрипта-мишени.…”

“…РНК-связывающие белки (RBP) способствуют посттранскрипционному контролю, влияя на стабильность и трансляцию мРНК при связывании с цис-элементами в транскрипте мРНК. RBP влияют на экспрессию генов через miRISC или его взаимодействие с мРНК-мишенью (52).…”