Regulation and different functions of the animal microRNA‐induced silencing complex

Abstract

Among the different types of small RNAs, microRNAs (miRNAs) are key players in controlling gene expression at the mRNA level. To be active, they must associate with an Argonaute protein to form the miRNA induced silencing complex (miRISC) and binds to specific mRNA through complementarity sequences. The miRISC binding to an mRNA can lead to multiple outcomes, the most frequent being inhibition of the translation and/or deadenylation followed by decapping and mRNA decay. In the last years, several studies described different mechanisms modulating miRISC functions in animals. For instance, the regulation of the Argonaute protein through post-translational modifications can change the miRISC gene regulatory activity as well as modulate its binding to proteins, mRNA targets and miRISC stability. Furthermore, the presence of RNA binding proteins and multiple miRISCs at the targeted mRNA 3 0 untranslated region (3 0 UTR) can also affect its function through cooperation or competition mechanisms, underlying the importance of the 3 0 UTR environment in miRNA-mediated repression. Another way to regulate the miRISC function is by modulation of its interactors, forming different types of miRNA silencing complexes that affect gene regulation differently. It is also reported that the subcellular localization of several components of the miRNA pathway can modulate miRISC function, suggesting an important role for vesicular trafficking in the regulation of this essential silencing complex.

Host miRNAs as biomarkers of SARS-CoV-2 infection: a critical review

“…Other members of this family are responsible for infections in humans, including the severe acute respiratory syndrome coronavirus the 3'untranslated region (3'UTR) of a messenger RNA (mRNA) and inhibit translation or induce degradation of this mRNA. [10][11][12] Biogenesis of miRNAs includes transcription by RNA polymerase II to pri-miRNAs that are further processed by Drosha giving rise to pre-miRNAs. Export to the cytoplasm is followed by Dicer processing, which generates miRNA duplexes that are loaded into an Argonaute protein to form a miRNA induced silencing complex (miRISC).…”

“…Export to the cytoplasm is followed by Dicer processing, which generates miRNA duplexes that are loaded into an Argonaute protein to form a miRNA induced silencing complex (miRISC). 12,13 miRNAs are involved in virtually all physiological and pathological processes, including viral infections and the antiviral immune response. 13 As discussed in some recent work, viral infections change the expression profile of cellular miRNAs (Fig.…”

RNA:RNA interaction in ternary complexes resolved by chemical probing

“…MicroRNAs (miRs) are small non-coding RNAs that regulate messenger RNA (mRNA) translation by either inhibiting protein translation or initiating mRNA degradation (Filipowicz, Bhattacharyya and Sonenberg, 2008;Frédérick and Simard, 2021). After maturation, the miR is loaded into the Argonaute protein (AGO) and forms the RNA-inducing silencing complex (RISC).…”

“…The interaction between miR loaded into AGO (miR-AGO) and the target mRNA initiates from the 5' seed region (Figure 1), then continues toward the 3'-end of miR, the compensatory region. Generally, the number of continuous canonical Watson-Crick (WC) base pairs in the seed determines the efficiency of mRNA down-regulation (Filipowicz, Bhattacharyya and Sonenberg, 2008;Bartel, 2018;Frédérick and Simard, 2021), while non-WC base-pairs for nucleotides 7 and 8 of the seed can reduce binding and down-regulation (Bartel, 2009;Agarwal et al, 2015). In rare cases, a strong interaction in the 3'-compensatory region can overcome the detrimental effect of mismatches in the seed region (Brennecke et al, 2005).…”

Integrative analysis of macrophage ribo-Seq and RNA-Seq data define glucocorticoid receptor regulated inflammatory response genes into distinct regulatory classes

“…For example, acute inflammatory responses may be suppressed by the rapid mRNA transcript degradation of cytokines, chemokines, enzymes, and other mediators [99] . Such post-transcriptional regulation is orchestrated by a diverse group of regulatory factors including RNA-binding proteins (RBP), microRNAs (miRNA) and other classes of small noncoding RNAs (sncRNA), which recognize and bind to sequences present in their target mRNAs [100] , [101] , [102] . Next generation sequencing methods such as RNA-seq, combined with ribo-seq, offers a quantitative approach to determine and understand the transcriptional and post-transcriptional gene regulation networks that GR acts within.…”