The RNA-induced silencing complex (RISC) is a key component of the RNA interference (RNAi) pathway, playing a central role in post-transcriptional gene regulation. RISC is primarily responsible for recognizing and targeting specific mRNA molecules for degradation or translational repression, principally through the action of small RNA molecules, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs). RISC is initially formed by the binding of a small RNA guide molecule—either a miRNA or siRNA—to one of its key components, Argonaute (AGO) proteins. This loading process is highly specific and ensures that only properly matured and complementary small RNAs are incorporated into the RISC complex. In the case of miRNAs, RISC is guided by mature miRNAs to target mRNAs that contain complementary sequences. These miRNAs are typically derived from longer primary transcripts, known as primary miRNAs (pri-miRNAs), which undergo several processing steps to generate mature miRNAs. When a miRNA within RISC recognizes a complementary sequence in the 3' untranslated region (UTR) of a target mRNA, it leads to translational repression and/or mRNA degradation. This prevents the translation of the target mRNA into a functional protein. miRNA-mediated gene regulation is essential for various cellular processes, including in differentiation and other developmental processes. In contrast to miRNAs, siRNAs are typically derived from exogenous sources, such as viral RNA or transposons. When cells are exposed to dsRNA, the enzyme Dicer processes it into siRNAs, which are then loaded into RISC. siRNAs then guide RISC to complementary sequences in target mRNAs, resulting in mRNA cleavage and degradation. This mechanism acts to provide a defence against viral infections and transposon mobilization. In some cases, RISC can cleave target mRNAs guided by siRNAs with perfect complementarity. This process is distinct from miRNA-mediated repression and results in the direct degradation of the target mRNA. Argonaute proteins are the central structural and functional components of the RISC complex. In humans, there are four Argonaute proteins (AGO1-4), with AGO2 noteworthy as it possesses endonuclease activity, allowing it to cleave target mRNAs with siRNA-like perfect complementarity. AGO proteins contain conserved PAZ, MID, and PIWI domains, which collectively interact with the loaded small RNA and facilitate target mRNA recognition, and in the case of AGO2, cleavage. The small RNA guide strand, either a miRNA or siRNA, is loaded into Argonaute. It provides the sequence specificity for target recognition and gene silencing. The guide strand is positioned within the MID and PIWI domains of Argonaute. RISC can contain additional accessory proteins that enhance its stability and functionality. These proteins can assist in target mRNA recognition, enhance RNA cleavage activity, or modulate RISC localization. An example is TRBP (TAR RNA-binding protein) in the context of siRNA-loaded RISC. RISC-mediated gene regulation involves extensive RNA-protein interactions. The small RNA guide strand within Argonaute interacts with the target mRNA, leading to translational repression or cleavage. Additionally, other proteins in the RISC complex and associated factors contribute to the stability and specificity of these interactions. We offer a wide product catalogue of research tools for studying RISC, including FMRP antibodies, and PIWIL1 antibodies. Explore our full RISC product range below and discover more, for less.